Researcher basic information

• PhD, Hokkaido University

• https://researchmap.jp/t-yokota?lang=en

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201501004840280625
• https://kaken.nii.ac.jp/d/r/90374321.ja.html

• 90374321

• 201501004840280625

• Meteolorogy
• Skeletal muscles and myokines
• Nutrition
• Atherosclerosis
• Telemedicine
• Ectopic fat
• Hybernation
• Sleep medicine
• Rehabilitation
• Genetic testing
• Data science
• Preventive medicine
• Hypertension
• ICT
• Digital health
• Sports medicine
• Exercise physiology
• Heart failure
• Mitochondria
• Gut microbiota
• Diabetes
• Oxidative stress

• Informatics, Life, health and medical informatics, Digital health
• Life Science, Cardiology
• Life Science, Sports sciences

Research activity information

• 2022, 大和証券ヘルス財団調査研究助成
  横田 卓
• 2017, Nakatomi Health Science Foundation Research Grant
  Takashi Yokota
• 2016, Hokkaido University President's Award
  Takashi Yokota
• 2015, Mochida Memorial Foundation for Medical and Pharmaceutical Research Grant
  Takashi Yokota
• 2012, Yutoukai Surgery Medicine Research Grant
  Takashi Yokota
• 2010, Manpei Suzuki Diabetes Foundation Study Abroad Scholarship
  Takashi Yokota

• Self-care interventions using mobile applications in heart failure management
  Takashi Yokota
  Journal of Cardiology, Elsevier BV, 24 Jul. 2026, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author], [International Magazine]
  English, Scientific journal
• Comment on "Associations between animal and plant protein intakes and the mortality and hospitalization of patients with chronic heart failure"
  Tasuku Inao; Yoichi M. Ito; Takashi Yokota; Arata Fukushima; Taisuke Ono; Takeshi Sota; Yoshiharu Kinugasa; Masashige Takahashi; Ryuichi Matsukawa; Ichiro Yoshida; Shigeo Kakinoki; Kazuya Yonezawa; Yoshihiro Himura; Isao Yokota; Kazuhiro Yamamoto; Miyuki Tsuchihashi-Makaya; Shintaro Kinugawa
  Clinical Nutrition ESPEN, 103404, 103404, Elsevier BV, 22 Jun. 2026, [Peer-reviewed], [Invited], [Corresponding author], [International Magazine]
  Scientific journal
• Associations between animal and plant protein intakes and the mortality and hospitalization of patients with chronic heart failure
  Tasuku Inao; Yoichi M. Ito; Takashi Yokota; Arata Fukushima; Taisuke Ono; Takeshi Sota; Yoshiharu Kinugasa; Masashige Takahashi; Ryuichi Matsukawa; Ichiro Yoshida; Shigeo Kakinoki; Kazuya Yonezawa; Yoshihiro Himura; Isao Yokota; Kazuhiro Yamamoto; Miyuki Tsuchihashi-Makaya; Shintaro Kinugawa
  Clinical Nutrition ESPEN, 73, 103307, 103307, Elsevier BV, Jun. 2026, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal
• Reduced hemoglobin-corrected diffusing capacity in pulmonary arterial hypertension with preserved pulmonary function and morphology
  Ayako Igarashi-Sugimoto; Ichizo Tsujino; Hideki Shima; Junichi Nakamura; Toshitaka Nakaya; Takahiro Sato; Taku Watanabe; Hiroshi Ohira; Kaoruko Shimizu; Takashi Yokota; Sari Iwasaki; Satonori Tsuneta; Isao Yokota; Satoshi Konno
  Respiratory Investigation, 63, 4, 600, 607, Elsevier BV, Jul. 2025, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal
• Reduction in Acetylation of Superoxide Dismutase 2 in Skeletal Muscle Improves Exercise Capacity in Mice With Heart Failure
  Tomoka Masunaga; Tomoyasu Suenaga; Shouji Matsushima; Toru Hashimoto; Shingo Takada; Eri Noda; Yoshizuki Fumoto; Soichiro Hata; Takashi Yokota; Shintaro Kinugawa
  Journal of Cachexia, Sarcopenia and Muscle, 16, 3, e13850, Wiley, Jun. 2025, [Peer-reviewed], [International Magazine]
  English, Scientific journal, ABSTRACT
  
  Background
  
  Skeletal muscle abnormalities, including mitochondrial dysfunction, play a crucial role in decreasing exercise capacity in patients with heart failure (HF). Although enhanced reactive oxygen species (ROS) production in skeletal muscle mitochondria has been implicated in skeletal muscle abnormalities, the underlying mechanisms have not been fully elucidated to date. Superoxide dismutase 2 (SOD2), an antioxidant enzyme present in mitochondria, is modified by acetylation, which reduces its activity. The aim of this study was to clarify whether reducing SOD2 acetylation by sirtuins 3 (SIRT3) activation improves skeletal muscle mitochondrial function and exercise capacity in HF model mice.
  
  Methods
  
  Myocardial infarction (MI) by ligation of the coronary artery or sham surgery was performed in male C57BL/6 J mice. Two weeks after surgery, these mice were treated with either the SIRT3 activator Honokiol (5 mg/kg body weight/day, i.p.) or vehicle. After 2 weeks of treatment, exercise capacity was evaluated by the treadmill test. Gastrocnemius muscle samples collected from the mice were used to measure mitochondrial function, as well as the levels of SIRT3, acetylated SOD2, and ROS production. Finally, the effect of adeno‐associated virus serotype 9 (AAV9)‐mediated overexpression of SIRT3 in the skeletal muscle on the exercise capacity of MI mice was investigated.
  
  Results
  
  MI mice showed decreased cardiac function and skeletal muscle weight, but Honokiol did not affect these. Exercise capacity was significantly decreased in MI mice compared with sham mice by 24.9%, and Honokiol treatment improved the exercise capacity of MI mice by 40.4% (p < 0.05). The mitochondrial oxygen consumption rate was impaired in MI mice, but was improved by Honokiol treatment. SIRT3 expression was decreased by 26.8%, and SOD2 acetylation was increased by 36.9% in the skeletal muscle of MI mice compared with sham (p < 0.05), and Honokiol treatment resulted in complete recovery of these levels (p < 0.05). Consistent with SOD2 acetylation, ROS production in the skeletal muscle was increased in MI mice and was ameliorated by Honokiol (p < 0.05). SIRT3 expression was increased in MI + AAV9‐SIRT3 mice compared with MI + AAV9‐Control mice. The overexpression of SIRT3 improved exercise capacity without altering cardiac function.
  
  Conclusions
  
  The SIRT3 activator Honokiol improved exercise capacity in MI model mice with HF, by improving mitochondrial function in skeletal muscle through the reduction of SOD2 acetylation. SIRT3 activation may thus be a novel therapeutic target for improving exercise capacity in patients with HF.
• Development and validation of an algorithm for identifying patients undergoing dialysis from patients with advanced chronic kidney disease
  Takahiro Imaizumi; Takashi Yokota; Kouta Funakoshi; Kazushi Yasuda; Akiko Hattori; Akemi Morohashi; Tatsumi Kusakabe; Masumi Shojima; Sayoko Nagamine; Toshiaki Nakano; Yong Huang; Hiroshi Morinaga; Miki Ohta; Satomi Nagashima; Ryusuke Inoue; Naoki Nakamura; Hideki Ota; Tatsuya Maruyama; Hideo Gobara; Akira Endoh; Masahiko Ando; Yoshimune Shiratori; Shoichi Maruyama
  Clinical and Experimental Nephrology, 29, 5, 650, 661, Springer Science and Business Media LLC, May 2025, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, Abstract
  
  Background
  
  Identifying patients on dialysis among those with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m² remains challenging. To facilitate clinical research in advanced chronic kidney disease (CKD) using electronic health records, we aimed to develop algorithms to identify dialysis patients using laboratory data obtained in routine practice.
  
  Methods
  
  We collected clinical data of patients with an eGFR < 15 mL/min/1.73 m² from six clinical research core hospitals across Japan: four hospitals for the derivation cohort and two for the validation cohort. The candidate factors for the classification models were identified using logistic regression with stepwise backward selection. To ensure transplant patients were not included in the non-dialysis population, we excluded individuals with the disease code Z94.0.
  
  Results
  
  We collected data from 1142 patients, with 640 (56%) currently undergoing hemodialysis or peritoneal dialysis (PD), including 426 of 763 patients in the derivation cohort and 214 of 379 patients in the validation cohort. The prescription of PD solutions perfectly identified patients undergoing dialysis. After excluding patients prescribed PD solutions, seven laboratory parameters were included in the algorithm. The areas under the receiver operation characteristic curve were 0.95 and 0.98 and the positive and negative predictive values were 90.9% and 91.4% in the derivation cohort and 96.2% and 94.6% in the validation cohort, respectively. The calibrations were almost linear.
  
  Conclusions
  
  We identified patients on dialysis among those with an eGFR < 15 ml/min/1.73 m². This study paves the way for database research in nephrology, especially for patients with non-dialysis-dependent advanced CKD.
• Contemporary clinical characteristics and management patterns in hypertrophic cardiomyopathy: insights from baseline enrolment data in a nationwide prospective Japanese registry
  Toru Kubo; Kenta Sugiura; Yukichi Tokita; Hitoshi Takano; Itaru Takamisawa; Morimasa Takayama; Yoshinori L Doi; Yuichiro Minami; Shota Shirotani; Mio Ebato; Miki Tsujiuchi; Takeru Nabeta; Takayuki Inomata; Takao Kato; Ryuji Okamoto; Kaoru Dohi; Yasuyoshi Takei; Taishiro Chikamori; Eiichi Watanabe; Azusa Furugen; Hirosato Doi; Keitaro Akita; Yuichiro Maekawa; Akiyoshi Ogimoto; Norio Tada; Takashi Yokota; Shuntaro Ikeda; Osamu Yamaguchi; Yasuhiro Izumiya; Atsushi Shibata; Seiji Takashio; Kenichi Tsujita; Yasuhiro Maejima; Noboru Fujino; Akihiro Nomura; Yuichi Akasaki; Koji Higuchi; Shuichi Fujita; Masaaki Hoshiga; Yasuyuki Shiraishi; Masaki Ieda; Yuya Miyamoto; Hiroaki Kitaoka
  Heart, 111, 18, 885, 892, BMJ, 04 Mar. 2025, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Background
  
  The Japanese Hypertrophic Cardiomyopathy Registry Study was designed to provide comprehensive, real-world insights into the clinical characteristics and management of hypertrophic cardiomyopathy (HCM) in Japan.
  
  Methods
  
  This multicentre, prospective study enrolled consecutive patients with HCM from 24 referral hospitals across Japan starting in 2016. The baseline characteristics of 1485 patients enrolled by December 2019 are presented in this analysis.
  
  Results
  
  The median ages at registration and diagnosis were 69 and 60 years, respectively, with men accounting for 54% of the cohort. Familial HCM was confirmed in 18% of cases. Of the cohort, 36% had hypertrophic obstructive cardiomyopathy (HOCM), while 8% had mid-ventricular obstruction, 14% had apical HCM and 4% were in the end-stage phase. Atrial fibrillation was observed in 27% of patients, though the majority were asymptomatic or had mild symptoms at registration. Adverse outcomes included prior sustained ventricular tachycardia or fibrillation (6%), heart failure requiring hospitalisation (11%) and embolic events (5%). Defibrillator implantation was performed in 11% of patients. Differences in the defibrillator indications for primary prevention in the current three guidelines and status of defibrillator deployment at registration were clarified: the percentages of class IIa recommendation in the whole cohort and of patients with defibrillator implantation in class IIa were 22% and 19% in the Japanese guidelines, 4% and 39% in the European guidelines and 28% and 22% in the American guidelines, respectively. Beta blockers were prescribed to 90% of patients with HOCM, while 51% received cibenzoline. Septal reduction therapies were performed in 22% of patients with HOCM, with 6% undergoing surgical myectomy.
  
  Conclusions
  
  As the first large-scale, prospective HCM registry in Japan, this study provides valuable baseline data on the clinical characteristics and management of HCM. These findings will help address gaps between current practice and guideline recommendations, improving the care of patients with HCM.
• Efficacy and safety of the urate-lowering agent febuxostat in chronic heart failure patients with hyperuricemia: results from the LEAF-CHF study
  Takashi Yokota; Shintaro Kinugawa; Arata Fukushima; Takahiro Okumura; Toyoaki Murohara; Hiroyuki Tsutsui
  Heart and Vessels, 40, 2, 111, 122, Springer Science and Business Media LLC, Feb. 2025, [Peer-reviewed], [Lead author, Corresponding author], [Domestic magazines]
  English, Scientific journal
• Associations of sarcopenia and malnutrition with 30-day in-hospital morbidity and mortality after cardiac surgery
  Takahiro Abe; Tasuku Inao; Yasushige Shingu; Akira Yamada; Shingo Takada; Arata Fukushima; Noriko Oyama-Manabe; Isao Yokota; Satoru Wakasa; Shintaro Kinugawa; Takashi Yokota
  European Journal of Cardio-Thoracic Surgery, 67, 1, ezae456, Oxford University Press (OUP), Jan. 2025, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, Abstract
  
  OBJECTIVES
  
  Sarcopenia and malnutrition often occur simultaneously in adults with cardiovascular diseases. Our objective was to determine the associations of preoperative sarcopenia and malnutrition with major adverse cardiac and cerebral events (MACCE) after cardiac surgery
  
  METHODS
  
  We retrospectively analyzed 154 consecutive patients who underwent elective cardiac surgery between January 2015 and June 2018 at two institutions in Japan. Sarcopenia and nutritional status were preoperatively assessed by bilateral psoas muscle volume index (PMVI) using CT scans and the prognostic nutritional index (PNI), respectively.
  
  RESULTS
  
  The median age in the total cohort was 69 years, and 43% were women. Within 30 days after surgery, 20 patients developed in-hospital MACCE and 7 patients died of any cause. Low PMVI (&lt;72.25 cm3/m2) and low PNI (&lt;48.15) were each independent predictors of postoperative MACCE occurrence with odds ratios (95% confidence interval) of 3.58 (1.22–10.53) and 3.73 (1.25–11.09) when adjusted for age and sex, and 3.25 (1.07–9.87) and 3.27 (1.08–9.89) when adjusted for preoperative left ventricular ejection fraction, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, and anticoagulant. In addition, the combination of low PMVI and low PNI conferred the highest risk of in-hospital MACCE among the 4 groups (ie, the low PMVI, low PNI, low PMVI+low PNI, and neither low PMVI nor low PNI groups).
  
  CONCLUSIONS
  
  Preoperative low PMVI and low PNI were respectively associated with 30-day in-hospital MACCE occurrence after cardiac surgery. Notably, coexistence of these reductions further enhanced the risk of postoperative MACCE.
• Associations of serum branched-chain amino acid and marine omega-3 fatty acid levels with exercise intolerance in heart failure patients
  Takeshi Sota; Yoshiharu Kinugasa; Natsuko Nakayama; Kensuke Nakamura; Masayuki Hirai; Masahiko Kato; Taisuke Ono; Masashige Takahashi; Hisashi Matsuo; Ryuichi Matsukawa; Ichiro Yoshida; Shigeo Kakinoki; Kazuya Yonezawa; Yoshihiro Himura; Takashi Yokota; Kazuhiro Yamamoto; Miyuki Tsuchihashi-Makaya; Shintaro Kinugawa
  Clinical Nutrition Open Science, 57, 241, 252, Elsevier BV, Oct. 2024, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Skeletal muscle mitochondria: A potential target for postmenopausal hormone replacement therapy
  Takashi Yokota
  Acta Physiologica, 240, 6, e14149, Wiley, 17 Apr. 2024, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author], [International Magazine]
  English, Scientific journal
• Influence of epicardial adipose tissue inflammation and adipocyte size on postoperative atrial fibrillation in patients after cardiovascular surgery
  Hiroyuki Natsui; Masaya Watanabe; Takashi Yokota; Satonori Tsuneta; Yoshizuki Fumoto; Haruka Handa; Matsushima Shouji; Jiro Koya; Kotaro Nishino; Daishiro Tatsuta; Takuya Koizumi; Takahide Kadosaka; Motoki Nakao; Taro Koya; Taro Temma; Yoichi M. Ito; Hatanaka C. Kanako; Yutaka Hatanaka; Shingu Yasushige; Satoru Wakasa; Shuhei Miura; Takahiko Masuda; Naritomo Nishioka; Shuichi Naraoka; Kayoko Ochi; Tomoko Kudo; Tsugumine Ishikawa; Toshihisa Anzai
  Physiological Reports, 12, 6, e15957, Wiley, 28 Mar. 2024, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Abstract
  
  Epicardial adipose tissue (EAT) is an active endocrine organ that is closely associated with occurrence of atrial fibrillation (AF). However, the role of EAT in the development of postoperative AF (POAF) remains unclear. We aimed to investigate the association between EAT profile and POAF occurrence in patients who underwent cardiovascular surgery. We obtained EAT samples from 53 patients to evaluate gene expression, histological changes, mitochondrial oxidative phosphorylation (OXPHOS) capacity in the EAT, and protein secretion in EAT‐conditioned medium. EAT volume was measured using computed tomography scan. Eighteen patients (34%) experienced POAF within 7 days after surgery. Although no significant difference was observed in EAT profile between patients with and without POAF, logistic regression analysis identified that the mRNA expression levels of tumor necrosis factor‐alpha (TNF‐α) were positively correlated and adipocyte size in the EAT was inversely correlated with onset of POAF, respectively. Mitochondrial OXPHOS capacity in the EAT was not associated with POAF occurrence; however, it showed an inverse correlation with adipocyte size and a positive correlation with adiponectin secretion. In conclusion, changes in the secretory profile and adipocyte morphology of the EAT, which represent qualitative aspects of the adipose tissue, were present before the onset of AF.
• Author Correction: Enhanced mitochondrial oxidative metabolism in peripheral blood mononuclear cells is associated with fatty liver in obese young adults
  Ryosuke Shirakawa; Takayuki Nakajima; Aya Yoshimura; Yukako Kawahara; Chieko Orito; Miwako Yamane; Haruka Handa; Shingo Takada; Takaaki Furihata; Arata Fukushima; Naoki Ishimori; Masao Nakagawa; Isao Yokota; Hisataka Sabe; Satoshi Hashino; Shintaro Kinugawa; Takashi Yokota
  Scientific Reports, 14, 1, 6786, Springer Science and Business Media LLC, 21 Mar. 2024, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Muscular stress is equal when resistance exercise with blood flow restriction is matched in total work volume: A cross‐sectional, cross‐over study
  Koichi Okita; Masashi Omokawa; Shingo Takada; Tomoyasu Kadoguchi; Noriteru Morita; Takashi Yokota
  Acta Physiologica, 240, 3, e14097, Wiley, 17 Jan. 2024, [Peer-reviewed], [Last author], [International Magazine]
  English, Scientific journal, Abstract
  
  Aim
  
  We compared muscular metabolic stress during exercise performed at multiple intensities, from very low to moderate, with blood flow restriction (BFR) adjusted by the same work volume.
  
  Methods
  
  Twenty‐five healthy young adults performed unilateral plantar flexion at 1 repetition/2 s in a magnetic resonance system. The BFR exercise protocols were as follows: (A) exercise with 10% of one repetition maximum (1‐RM) for 360 s, (B) 15% 1‐RM for 240 s, (C) 20% 1‐RM for 180 s, (D) 30% 1‐RM for 120 s, and (E) 40% 1‐RM for 90 s. All protocols had the same total work volume (load × repetitions = 1800). A high‐intensity protocol at 65% 1‐RM without BFR (60 s) was also performed for comparison. We used ³¹P‐magnetic resonance spectroscopy to evaluate the muscular metabolic stress in the subjects' calf muscle, defined as decreases in phosphocreatine and intramuscular pH.
  
  Results
  
  The phosphocreatine depletion (A: 15.6 ± 0.7, B: 14.8 ± 0.8, C: 15.2 ± 0.6, D: 14.3 ± 0.6, E: 10.9 ± 0.5 mM; no significant difference [ns]) and the intramuscular pH decrease (A: 6.82 ± 0.02, B: 6.84 ± 0.01, C: 6.83 ± 0.02, D: 6.83 ± 0.02, E: 6.77 ± 0.02; ns) at the end of each exercise were similar and greater than those produced by the 65% 1‐RM without BFR.
  
  Conclusion
  
  If the total work volumes are equal, the metabolic stress in exercising muscle may reach similar levels at the end of exercise with BFR and could provide similar successful training effects.
• The AppCare-HF randomized clinical trial: a feasibility study of a novel self-care support mobile app for individuals with chronic heart failure
  Takashi Yokota; Arata Fukushima; Miyuki Tsuchihashi-Makaya; Takahiro Abe; Shingo Takada; Takaaki Furihata; Naoki Ishimori; Takeo Fujino; Shintaro Kinugawa; Masayuki Ohta; Shigeo Kakinoki; Isao Yokota; Akira Endoh; Masanori Yoshino; Hiroyuki Tsutsui
  European Heart Journal - Digital Health, 4, 4, 325, 336, Oxford University Press (OUP), 10 May 2023, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
  English, Scientific journal, Abstract
  
  Aims
  
  We evaluated a self-care intervention with a novel mobile application (app) in chronic heart failure (HF) patients. To facilitate patient-centred care in HF management, we developed a self-care support mobile app to boost HF patients’ optimal self-care.
  
  Methods and results
  
  We conducted a multicentre, randomized, controlled study evaluating the feasibility of the self-care support mobile app designed for use by HF patients. The app consists of a self-monitoring assistant, education, and automated alerts of possible worsening HF. The intervention group received a tablet personal computer (PC) with the self-care support app installed, and the control group received a HF diary. All patients performed self-monitoring at home for 2 months. Their self-care behaviours were evaluated by the European Heart Failure Self-Care Behaviour Scale. We enrolled 24 outpatients with chronic HF (ages 31–78 years; 6 women, 18 men) who had a history of HF hospitalization. During the 2 month study period, the intervention group (n = 13) showed excellent adherence to the self-monitoring of each vital sign, with a median [interquartile range (IQR)] ratio of self-monitoring adherence for blood pressure, body weight, and body temperature at 100% (92–100%) and for oxygen saturation at 100% (91–100%). At 2 months, the intervention group’s self-care behaviour score was significantly improved compared with the control group (n = 11) [median (IQR): 16 (16–22) vs. 28 (20–36), P = 0.02], but the HF Knowledge Scale, the General Self-Efficacy Scale, and the Short Form-8 Health Survey scores did not differ between the groups.
  
  Conclusion
  
  The novel mobile app for HF is feasible.
• Enhanced mitochondrial oxidative metabolism in peripheral blood mononuclear cells is associated with fatty liver in obese young adults
  Ryosuke Shirakawa; Takayuki Nakajima; Aya Yoshimura; Yukako Kawahara; Chieko Orito; Miwako Yamane; Haruka Handa; Shingo Takada; Takaaki Furihata; Arata Fukushima; Naoki Ishimori; Masao Nakagawa; Isao Yokota; Hisataka Sabe; Satoshi Hashino; Shintaro Kinugawa; Takashi Yokota
  Scientific Reports, 13, 1, 5203, 5203, Springer Science and Business Media LLC, 30 Mar. 2023, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, Abstract
  
  Systemic inflammation underlies the association between obesity and nonalcoholic fatty liver disease (NAFLD). Here, we investigated functional changes in leukocytes’ mitochondria in obese individuals and their associations with NAFLD. We analyzed 14 obese male Japanese university students whose body mass index was > 30 kg/m² and 15 healthy age- and sex-matched lean university students as controls. We observed that the mitochondrial oxidative phosphorylation (OXPHOS) capacity with complex I + II-linked substrates in peripheral blood mononuclear cells (PBMCs), which was measured using a high-resolution respirometry, was significantly higher in the obese group versus the controls. The PBMCs’ mitochondrial complex IV capacity was also higher in the obese subjects. All of the obese subjects had hepatic steatosis defined by a fatty liver index (FLI) score ≥ 60, and there was a positive correlation between their FLI scores and their PBMCs’ mitochondrial OXPHOS capacity. The increased PBMCs’ mitochondrial OXPHOS capacity was associated with insulin resistance, systemic inflammation, and higher serum levels of interleukin-6 in the entire series of subjects. Our results suggest that the mitochondrial respiratory capacity is increased in the PBMCs at the early stage of obesity, and the enhanced PBMCs’ mitochondrial oxidative metabolism is associated with hepatic steatosis in obese young adults.
• Empagliflozin suppresses mitochondrial reactive oxygen species generation and mitigates the inducibility of atrial fibrillation in diabetic rats
  Takuya Koizumi; Masaya Watanabe; Takashi Yokota; Masumi Tsuda; Haruka Handa; Jiro Koya; Kotaro Nishino; Daishiro Tatsuta; Hiroyuki Natsui; Takahide Kadosaka; Taro Koya; Motoki Nakao; Hikaru Hagiwara; Rui Kamada; Taro Temma; Shinya Tanaka; Toshihisa Anzai
  Frontiers in Cardiovascular Medicine, 10, 1005408, 1005408, Frontiers Media SA, 06 Feb. 2023, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Introduction
  
  Recent studies have demonstrated that sodium-glucose co-transporter-2 inhibitors (SGLT2-i) reduce the risk of atrial fibrillation (AF) in patients with diabetes mellitus (DM), in which oxidative stress due to increased reactive oxygen species (ROS) contributes to the pathogenesis of AF. We aimed to further investigate this, and examine whether the SGLT2-i empagliflozin suppresses mitochondrial-ROS generation and mitigates fibrosis.
  
  Methods
  
  A high-fat diet and low-dose streptozotocin treatment were used to induce type-2 DM (T2DM) in Sprague-Dawley rats. The rats were randomly divided into three groups: control, DM, and DM treated with empagliflozin (30 mg/kg/day) for 8 weeks. The mitochondrial respiratory capacity and ROS generation in the atrial myocardium were measured using a high-resolution respirometer. Oxidative stress markers and protein expression related to mitochondrial biogenesis and dynamics as well as the mitochondrial morphology were examined in the atrial tissue. Additionally, mitochondrial function was examined in H9c2 cardiomyoblasts. Atrial tachyarrhythmia (ATA) inducibility, interatrial conduction time (IACT), and fibrosis were also measured.
  
  Results
  
  Inducibility of ATA, fibrosis, and IACT were increased in rats with DM when compared to controls, all of which were restored by empagliflozin treatment. In addition, the rats with DM had increased mitochondrial-ROS with an impaired complex I-linked oxidative phosphorylation capacity. Importantly, empagliflozin seemed to ameliorate these impairments in mitochondrial function. Furthermore, empagliflozin reversed the decrease in phosphorylated AMPK expression and altered protein levels related to mitochondrial biogenesis and dynamics, and increased mitochondrial content. Empagliflozin also improved mitochondrial function in H9c2 cells cultured with high glucose medium.
  
  Discussion
  
  These data suggest that empagliflozin has a cardioprotective effect, at least in part, by reducing mitochondrial ROS generation through AMPK signaling pathways in the atrium of diabetic rats. This suggests that empagliflozin might suppress the development of AF in T2DM.
• Luseogliflozin preserves the pancreatic beta-cell mass and function in db/db mice by improving mitochondrial function
  Yuki Yamauchi; Akinobu Nakamura; Takashi Yokota; Kiyohiko Takahashi; Shinichiro Kawata; Kazuhisa Tsuchida; Kazuno Omori; Hiroshi Nomoto; Hiraku Kameda; Kyu Yong Cho; Toshihisa Anzai; Shinya Tanaka; Yasuo Terauchi; Hideaki Miyoshi; Tatsuya Atsumi
  Scientific Reports, 12, 1, 9740, 9740, Springer Science and Business Media LLC, Dec. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Abstract
  
  We aimed to determine the mechanism by which the sodium glucose co-transporter 2 inhibitor, luseogliflozin, preserves pancreatic beta-cell mass and function in db/db mice. Six-week-old db/db mice were fed to standard chow or standard chow containing 0.01% luseogliflozin. After 4 weeks, DNA microarray analysis, real-time PCR analysis, and measurement of mitochondrial respiratory capacity and reactive oxygen species (ROS) generation were performed using isolated islets. Immunohistochemistry and electron microscopic analysis were performed using pancreatic tissues. Metabolites extracted from the islets were measured by capillary electrophoresis mass spectrometry. The expression of genes involved in the tricarboxylic acid (TCA) cycle and electron transport chain was upregulated by luseogliflozin. Luseogliflozin improved the mitochondrial complex II-linked oxidative phosphorylation capacity and reduced ROS generation. Mitochondrial morphology was normally maintained by luseogliflozin. Luseogliflozin increased NK6 homeobox 1 (NKX6.1) expression and TCA cycle metabolites. Relief of glucotoxicity by luseogliflozin may involve lower mitochondrial ROS generation and an improvement in complex II-linked mitochondrial respiration. Reducing ROS generation through preventing complex II damage likely increases NKX6.1 expression and ameliorate glucose metabolism in the TCA cycle, contributing to the protection of pancreatic beta-cells. Protection of complex II in pancreatic beta-cells represents a novel therapeutic target for type 2 diabetes.
• Cross-disease communication between cancer and heart failure provides a rational approach to prevention and treatment of both diseases
  Shingo Takada; Shintaro Kinugawa; Haruka Handa; Takashi Yokota; Hisataka Sabe
  Frontiers in Oncology, 12, 1006322, 1006322, Frontiers Media SA, 31 Oct. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Accumulating clinical data have demonstrated a clear positive association between cancer and cardiac disorders, particularly chronic heart failure (CHF). These two diseases can be mutual drivers of each other, and hence frequently co-occur in patients. The immune system is the core mechanism that eliminates transformed cells from our bodies. However, immune cells often play distinct or even conflicting roles in cancer and CHF. Moreover, CHF alters the properties of immune cells, particularly those of regulatory T cells. Our previous study showed that the oxidative phosphorylation capacity of peripheral blood mononuclear cells is impaired in CHF, leading to the increased production of reactive oxygen species. Therefore, the co-occurrence of cancer and CHF becomes a serious problem, affecting the treatment of both diseases, and consequently negatively affecting patient survival rates. To date, few methods have been identified that effectively treat both diseases at the same time. Mitochondria activity may change in immune cells during their activation and exhaustion, and in CHF. Mitochondria activity is also largely affected in myocardia in CHF. We here focus on the mitochondrial abnormalities of immune cells in cancer and CHF, and discuss possible ways to treat cancer and CHF at the same time by targeting mitochondrial abnormalities. Many cancer cells are inevitably produced daily in our bodies, mostly owing to enzymatic nucleotide errors of DNA replication and repair. Therefore, the possibility of ways to prevent cancer by preventing the onset of heart failure will also be discussed.
• Succinyl-CoA-based energy metabolism dysfunction in chronic heart failure
  Shingo Takada; Satoshi Maekawa; Takaaki Furihata; Naoya Kakutani; Daiki Setoyama; Koji Ueda; Hideo Nambu; Hikaru Hagiwara; Haruka Handa; Yoshizuki Fumoto; Soichiro Hata; Tomoka Masunaga; Arata Fukushima; Takashi Yokota; Dongchon Kang; Shintaro Kinugawa; Hisataka Sabe
  Proc Natl Acad Sci U S A, 119, 41, e2203628119, Proceedings of the National Academy of Sciences, 11 Oct. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Heart failure (HF) is a leading cause of death and repeated hospitalizations and often involves cardiac mitochondrial dysfunction. However, the underlying mechanisms largely remain elusive. Here, using a mouse model in which myocardial infarction (MI) was induced by coronary artery ligation, we show the metabolic basis of mitochondrial dysfunction in chronic HF. Four weeks after ligation, MI mice showed a significant decrease in myocardial succinyl-CoA levels, and this decrease impaired the mitochondrial oxidative phosphorylation (OXPHOS) capacity. Heme synthesis and ketolysis, and protein levels of several enzymes consuming succinyl-CoA in these events, were increased in MI mice, while enzymes synthesizing succinyl-CoA from α-ketoglutarate and glutamate were also increased. Furthermore, the ADP-specific subunit of succinyl-CoA synthase was reduced, while its GDP-specific subunit was almost unchanged. Administration of 5-aminolevulinic acid, an intermediate in the pathway from succinyl-CoA to heme synthesis, appreciably restored succinyl-CoA levels and OXPHOS capacity and prevented HF progression in MI mice. Previous reports also suggested the presence of succinyl-CoA metabolism abnormalities in cardiac muscles of HF patients. Our results identified that changes in succinyl-CoA usage in different metabolisms of the mitochondrial energy production system is characteristic to chronic HF, and although similar alterations are known to occur in healthy conditions, such as during strenuous exercise, they may often occur irreversibly in chronic HF leading to a decrease in succinyl-CoA. Consequently, nutritional interventions compensating the succinyl-CoA consumption are expected to be promising strategies to treat HF.
• Empagliflozin improves cardiac mitochondrial function and survival through energy regulation in a murine model of heart failure
  Aya Shiraki; Jun-ichi Oyama; Takahiko Shimizu; Takayuki Nakajima; Takashi Yokota; Koichi Node
  European Journal of Pharmacology, 931, 175194, 175194, Elsevier BV, Aug. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Diagnostic performance of nutritional indicators in patients with heart failure
  Yoshiharu Kinugasa; Takeshi Sota; Hiroko Kamitani; Natsuko Nakayama; Kensuke Nakamura; Masayuki Hirai; Kiyotaka Yanagihara; Masahiko Kato; Taisuke Ono; Masashige Takahashi; Hisashi Matsuo; Ryuichi Matsukawa; Ichiro Yoshida; Shigeo Kakinoki; Kazuya Yonezawa; Yoshihiro Himura; Takashi Yokota; Kazuhiro Yamamoto; Miyuki Tsuchihashi‐Makaya; Shintaro Kinugawa
  ESC Heart Failure, 9, 4, 2096, 2106, Wiley, Aug. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Impact of citrus fruit intake on the mental health of patients with chronic heart failure
  Naoya Kakutani; Takashi Yokota; Arata Fukushima; Yoshikuni Obata; Taisuke Ono; Takeshi Sota; Yoshiharu Kinugasa; Masashige Takahashi; Hisashi Matsuo; Ryuichi Matsukawa; Ichiro Yoshida; Shigeo Kakinoki; Kazuya Yonezawa; Yoshihiro Himura; Isao Yokota; Kazuhiro Yamamoto; Miyuki Tsuchihashi-Makaya; Shintaro Kinugawa
  Journal of Cardiology, 79, 6, 719, 726, Elsevier BV, Jun. 2022, [Peer-reviewed], [Corresponding author], [Domestic magazines]
  English, Scientific journal, BACKGROUND: The full impact of the intake of citrus fruits on the risk of depression in individuals with chronic heart failure (HF) is unknown. Here, we examined the associations between the estimated habitual intakes of citrus fruits and depressive symptoms in patients with chronic HF. METHODS: We enrolled 150 stable outpatients with chronic HF who had a history of worsening HF. To assess the patients' daily dietary patterns, we used a brief self-administered diet-history questionnaire to calculate the daily consumption of foods and nutrients. To assess the patients' mental state, we used a nine-item Patient Health Questionnaire (PHQ-9). RESULTS: Twelve patients (8%) were identified as having moderate-to-severe depression (PHQ-9 score ≥10). The patients with PHQ-9 ≥10 had lower daily intakes of citrus fruits compared to those with no or mild depressive symptoms (PHQ-9 <10). The daily intakes of various antioxidants, including vitamin C, β-carotene, and β-cryptoxanthin, all of which are abundant in citrus fruits, were reduced in the patients with PHQ-9 ≥10, accompanied by higher serum levels of 8-isoprostane (an oxidative stress marker). A multivariate logistic regression analysis using forward selection showed that a lowered daily intake of citrus fruits was an independent predictor of the comorbidity of moderate-to-severe depression in patients with chronic HF, after adjustment for age, gender, and the hemoglobin value. CONCLUSIONS: A lower daily consumption of citrus fruits was associated with higher prevalence of depression in patients with chronic HF. Our findings support the hypothesis that a daily consumption of citrus fruits has a beneficial effect on the prevention and treatment of depression in chronic HF patients.
• Genome-wide CRISPR screen identifies CDK6 as a therapeutic target in adult T-cell leukemia/lymphoma
  Takashi Ishio; Sarvesh Kumar; Joji Shimono; Anusara Daenthanasanmak; Sigrid Dubois; Yuquan Lin; Bonita Bryant; Michael N. Petrus; Emmanuel Bachy; Da Wei Huang; Yandan Yang; Patrick L. Green; Hiroo Hasegawa; Michiyuki Maeda; Hideki Goto; Tomoyuki Endo; Takashi Yokota; Kanako C. Hatanaka; Yutaka Hatanaka; Shinya Tanaka; Yoshihiro Matsuno; Yibin Yang; Satoshi Hashino; Takanori Teshima; Thomas A. Waldmann; Louis M. Staudt; Masao Nakagawa
  Blood, 139, 10, 1541, 1556, American Society of Hematology, 10 Mar. 2022, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal,
  Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis with current therapy. Here we report genome-wide CRISPR-Cas9 screening of ATLL models, which identified CDK6, CCND2, BATF3, JUNB, STAT3, and IL10RB as genes that are essential for the proliferation and/or survival of ATLL cells. As a single agent, the CDK6 inhibitor palbociclib induced cell cycle arrest and apoptosis in ATLL models with wild-type TP53. ATLL models that had inactivated TP53 genetically were relatively resistant to palbociclib owing to compensatory CDK2 activity, and this resistance could be reversed by APR-246, a small molecule activator of mutant TP53. The CRISPR-Cas9 screen further highlighted the dependence of ATLL cells on mTORC1 signaling. Treatment of ATLL cells with palbociclib in combination with mTORC1 inhibitors was synergistically toxic irrespective of the TP53 status. This work defines CDK6 as a novel therapeutic target for ATLL and supports the clinical evaluation of palbociclib in combination with mTORC1 inhibitors in this recalcitrant malignancy.
• Loeys-Dietz Cardiomyopathy? Long-term Follow-up After Onset of Acute Decompensated Heart Failure
  Takashi Yokota; Hiroaki Koiwa; Shouji Matsushima; Shingo Tsujinaga; Masanao Naya; Hiroko Morisaki; Takayuki Morisaki
  Canadian Journal of Cardiology, 38, 3, 389, 391, Elsevier BV, Mar. 2022, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
  English, Scientific journal
• Premedication with pioglitazone prevents doxorubicin-induced left ventricular dysfunction in mice
  Takaaki Furihata; Satoshi Maekawa; Shingo Takada; Naoya Kakutani; Hideo Nambu; Ryosuke Shirakawa; Takashi Yokota; Shintaro Kinugawa
  BMC Pharmacology and Toxicology, 22, 1, 27, Springer Science and Business Media LLC, Dec. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Abstract
  
  Background
  
  Doxorubicin (DOX) is widely used as an effective chemotherapeutic agent for cancers; however, DOX induces cardiac toxicity, called DOX-induced cardiomyopathy. Although DOX-induced cardiomyopathy is known to be associated with a high cumulative dose of DOX, the mechanisms of its long-term effects have not been completely elucidated. Pioglitazone (Pio) is presently contraindicated in patients with symptomatic heart failure owing to the side effects. The concept of drug repositioning led us to hypothesize the potential effects of Pio as a premedication before DOX treatment, and to analyze this hypothesis in mice.
  
  Methods
  
  First, for the hyperacute (day 1) and acute (day 7) DOX-induced dysfunction models, mice were fed a standard diet with or without 0.02% (wt/wt) Pio for 5 days before DOX treatment (15 mg/kg body weight [BW] via intraperitoneal [i.p.] administration). The following 3 treatment groups were analyzed: standard diet + vehicle (Vehicle), standard diet + DOX (DOX), and Pio + DOX. Next, for the chronic model (day 35), the mice were administrated DOX once a week for 5 weeks (5 mg/kg BW/week, i.p.).
  
  Results
  
  In the acute phase after DOX treatment, the percent fractional shortening of the left ventricle (LV) was significantly decreased in DOX mice. This cardiac malfunction was improved in Pio + DOX mice. In the chronic phase, we observed that LV function was preserved in Pio + DOX mice.
  
  Conclusions
  
  Our findings may provide a new pathophysiological explanation by which Pio plays a role in the treatment of DOX-induced cardiomyopathy, but the molecular links between Pio and DOX-induced LV dysfunction remain largely elusive.
• Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients
  Takashi Yokota; Shintaro Kinugawa; Kagami Hirabayashi; Mayumi Yamato; Shingo Takada; Tadashi Suga; Ippei Nakano; Arata Fukushima; Shouji Matsushima; Koichi Okita; Hiroyuki Tsutsui
  Scientific Reports, 11, 1, Springer Science and Business Media LLC, Dec. 2021, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
  English, Scientific journal, Oxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO₂) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by ³¹phosphorus- and ¹proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.
• Cardiac-specific loss of mitoNEET expression is linked with age-related heart failure
  Takaaki Furihata; Shingo Takada; Naoya Kakutani; Satoshi Maekawa; Masaya Tsuda; Junichi Matsumoto; Wataru Mizushima; Arata Fukushima; Takashi Yokota; Nobuyuki Enzan; Shouji Matsushima; Haruka Handa; Yoshizuki Fumoto; Junko Nio-Kobayashi; Toshihiko Iwanaga; Shinya Tanaka; Hiroyuki Tsutsui; Hisataka Sabe; Shintaro Kinugawa
  Communications Biology, 4, 1, Springer Science and Business Media LLC, Dec. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Heart failure (HF) occurs frequently among older individuals, and dysfunction of cardiac mitochondria is often observed. We here show the cardiac-specific downregulation of a certain mitochondrial component during the chronological aging of mice, which is detrimental to the heart. MitoNEET is a mitochondrial outer membrane protein, encoded by CDGSH iron sulfur domain 1 (CISD1). Expression of mitoNEET was specifically downregulated in the heart and kidney of chronologically aged mice. Mice with a constitutive cardiac-specific deletion of CISD1 on the C57BL/6J background showed cardiac dysfunction only after 12 months of age and developed HF after 16 months; whereas irregular morphology and higher levels of reactive oxygen species in their cardiac mitochondria were observed at earlier time points. Our results suggest a possible mechanism by which cardiac mitochondria may gradually lose their integrity during natural aging, and shed light on an uncharted molecular basis closely related to age-associated HF.
• A Brief, Individualized Exercise Program at Intensities Below the Ventilatory Threshold Exerts Therapeutic Effects for Depression: A Pilot Study
  Yuri Sakai; Chong Chen; Atsuhito Toyomaki; Naoki Hashimoto; Kan Kitagawa; Takao Inoue; Asumi Sato; Keisuke Makihara; Rie Kameyama; Yumi Wakatsuki; Niki Udo; Ryosuke Shirakawa; Takashi Yokota; Shin Nakagawa; Ichiro Kusumi
  Frontiers in Behavioral Neuroscience, 15, 787688, 787688, Frontiers Media SA, 22 Nov. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Due to the fact that existing pharmacological treatments for depression are not ideal, effort has been devoted to the development of complementary, alternative therapies such as physical exercise. The antidepressant effect of exercise is well documented. However, current recommendations and prescriptions of exercise may be too demanding for depressed patients, as some complain about the design of exercise programs and depression is associated with reduced motivation and capacity to exercise. Therefore, appropriately designed, patient-friendly exercise programs may prove critical for the long-term maintenance and therapeutic effects of exercise. In this pilot study, we developed an exercise program based on patients’ individual level of ventilatory threshold (VT), a submaximal index of aerobic capacity measured by Cardiopulmonary Exercise Testing (CPX). Compared to traditional measures, CPX provides more trustable indices of aerobic capacity and more homogenous exercise prescriptions. The main episode of the program consisted of 15–25 min of cycling twice a week at an intensity that approached but never went higher than subjects’ VT (considered low to moderate in intensity). We found that in patients diagnosed with major depressive disorder or persistent depressive disorder (n = 8), the program resulted in a significant reduction in depressive symptoms at week 8, which was maintained at week 16. Meanwhile, patients’ social functioning, quality of life, and cognitive functions improved. Although we used a single arm, non-randomized design, our results suggest that even a brief, low to moderate intensity exercise program may exert therapeutic effects for depression and CPX may be a useful tool for exercise prescriptions.
• Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice
  Yoshinori Ohmura; Naoki Ishimori; Akimichi Saito; Takashi Yokota; Shunpei Horii; Satoshi Tokuhara; Kazuya Iwabuchi; Hiroyuki Tsutsui
  International Journal of Molecular Sciences, 22, 22, 12451, 12451, MDPI AG, 18 Nov. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, The infiltration and activation of macrophages as well as lymphocytes within atherosclerotic lesion contribute to the pathogenesis of plaque rupture. We have demonstrated that invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that recognize glycolipid antigens, play a crucial role in atherogenesis. However, it remained unclear whether iNKT cells are also involved in plaque instability. Apolipoprotein E (apoE) knockout mice were fed a standard diet (SD) or a high-fat diet (HFD) for 8 weeks. Moreover, the SD- and the HFD-fed mice were divided into two groups according to the intraperitoneal injection of α-galactosylceramide (αGC) that specifically activates iNKT cells or phosphate-buffered saline alone (PBS). ApoE/Jα18 double knockout mice, which lack iNKT cells, were also fed an SD or HFD. Plaque instability was assessed at the brachiocephalic artery by the histological analysis. In the HFD group, αGC significantly enhanced iNKT cell infiltration and exacerbated atherosclerotic plaque instability, whereas the depletion of iNKT cells attenuated plaque instability compared to PBS-treated mice. Real-time PCR analyses in the aortic tissues showed that αGC administration significantly increased expressional levels of inflammatory genes such as IFN-γ and MMP-2, while the depletion of iNKT cells attenuated these expression levels compared to those in the PBS-treated mice. Our findings suggested that iNKT cells are involved in the exacerbation of plaque instability via the activation of inflammatory cells and upregulation of MMP-2 in the vascular tissues.
• Angiotensin‐converting enzyme inhibitor prevents skeletal muscle fibrosis in diabetic mice
  Naoya Kakutani; Shingo Takada; Hideo Nambu; Satoshi Maekawa; Hikaru Hagiwara; Katsuma Yamanashi; Yoshikuni Obata; Ippei Nakano; Yoshizuki Fumoto; Soichiro Hata; Takaaki Furihata; Arata Fukushima; Takashi Yokota; Shintaro Kinugawa
  Experimental Physiology, 106, 8, 1785, 1793, Wiley, Aug. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, NEW FINDINGS: What is the central question of this study? We questioned whether an angiotensin-converting enzyme (ACE) inhibitor prevents skeletal muscle fibrosis in diabetic mice. What is the main finding and its importance? Administration of ACE inhibitor prevents the increase in skeletal muscle fibrosis during the early phase after induction of diabetes by streptozotocin. Our findings might provide a new therapeutic target for skeletal muscle abnormalities in diabetes. ABSTRACT: Fibrosis is characterized by the excessive production and accumulation of extracellular matrix components, including collagen. Although the extracellular matrix is an essential component of skeletal muscle, fibrosis can have negative effects on muscle function. Skeletal muscle fibrosis was shown to be increased in spontaneously hypertensive rats and to be prevented by an angiotensin-converting enzyme (ACE) inhibitor, an antihypertensive drug, in dystrophic mice or a mouse model of myocardial infarction. In this study, we therefore analysed whether (1) there is increased skeletal muscle fibrosis in streptozotocin (STZ)-induced diabetic mice, and (2) a preventive effect on skeletal muscle fibrosis by administration of an ACE inhibitor. Skeletal muscle fibrosis was significantly increased in STZ-induced diabetic mice compared with control mice from 2 to 14 days post-STZ. The ACE inhibitor prevented both skeletal muscle fibrosis and the reduction in muscle function in STZ-treated mice. Our study demonstrated that administration of an ACE inhibitor prevents the increase in skeletal muscle fibrosis during the early phase after onset of diabetes. Our findings might provide a new therapeutic target for skeletal muscle abnormalities in diabetes. Future studies are required to clarify whether skeletal muscle fibrosis is also linked directly to physical activity.
• Impact of Inadequate Calorie Intake on Mortality and Hospitalization in Stable Patients with Chronic Heart Failure
  Yoshikuni Obata; Naoya Kakutani; Shintaro Kinugawa; Arata Fukushima; Takashi Yokota; Shingo Takada; Taisuke Ono; Takeshi Sota; Yoshiharu Kinugasa; Masashige Takahashi; Hisashi Matsuo; Ryuichi Matsukawa; Ichiro Yoshida; Isao Yokota; Kazuhiro Yamamoto; Miyuki Tsuchihashi-Makaya
  Nutrients, 13, 3, 874, 874, MDPI AG, 08 Mar. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Malnutrition is highly prevalent in patients with heart failure (HF), but the precise impact of dietary energy deficiency on HF patients’ clinical outcomes is not known. We investigated the associations between inadequate calorie intake and adverse clinical events in 145 stable outpatients with chronic HF who had a history of hospitalization due to worsening HF. To assess the patients’ dietary pattern, we used a brief self-administered diet-history questionnaire (BDHQ). Inadequate calorie intake was defined as <60% of the estimated energy requirement. In the total chronic HF cohort, the median calorie intake was 1628 kcal/day. Forty-four patients (30%) were identified as having an inadequate calorie intake. A Kaplan–Meier analysis revealed that the patients with inadequate calorie intake had significantly worse clinical outcomes including all-cause death and HF-related hospitalization during the 1-year follow-up period versus those with adequate calorie intake (20% vs. 5%, p < 0.01). A multivariate logistic regression analysis showed that inadequate calorie intake was an independent predictor of adverse clinical events after adjustment for various factors that may influence patients’ calorie intake. Among patients with chronic HF, inadequate calorie intake was associated with an increased risk of all-cause mortality and rehospitalization due to worsening HF. However, our results are preliminary and larger studies with direct measurements of dietary calorie intake and total energy expenditure are needed to clarify the intrinsic nature of this relationship.
• Inhibition of xanthine oxidase in the acute phase of myocardial infarction prevents skeletal muscle abnormalities and exercise intolerance
  Hideo Nambu; Shingo Takada; Satoshi Maekawa; Junichi Matsumoto; Naoya Kakutani; Takaaki Furihata; Ryosuke Shirakawa; Takashi Katayama; Takayuki Nakajima; Katsuma Yamanashi; Yoshikuni Obata; Ippei Nakano; Masaya Tsuda; Akimichi Saito; Arata Fukushima; Takashi Yokota; Junko Nio-Kobayashi; Hironobu Yasui; Kei Higashikawa; Yuji Kuge; Toshihisa Anzai; Hisataka Sabe; Shintaro Kinugawa
  Cardiovascular Research, 117, 3, 805, 819, Oxford University Press (OUP), 22 Feb. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal,
  
  
  Exercise intolerance in patients with heart failure (HF) is partly attributed to skeletal muscle abnormalities. We have shown that reactive oxygen species (ROS) play a crucial role in skeletal muscle abnormalities, but the pathogenic mechanism remains unclear. Xanthine oxidase (XO) is reported to be an important mediator of ROS overproduction in ischaemic tissue. Here, we tested the hypothesis that skeletal muscle abnormalities in HF are initially caused by XO-derived ROS and are prevented by the inhibition of their production.
  
  
  
  
  
  Myocardial infarction (MI) was induced in male C57BL/6J mice, which eventually led to HF, and a sham operation was performed in control mice. The time course of XO-derived ROS production in mouse skeletal muscle post-MI was first analysed. XO-derived ROS production was significantly increased in MI mice from Days 1 to 3 post-surgery (acute phase), whereas it did not differ between the MI and sham groups from 7 to 28 days (chronic phase). Second, mice were divided into three groups: sham + vehicle (Sham + Veh), MI + vehicle (MI + Veh), and MI + febuxostat (an XO inhibitor, 5 mg/kg body weight/day; MI + Feb). Febuxostat or vehicle was administered at 1 and 24 h before surgery, and once-daily on Days 1–7 post-surgery. On Day 28 post-surgery, exercise capacity and mitochondrial respiration in skeletal muscle fibres were significantly decreased in MI + Veh compared with Sham + Veh mice. An increase in damaged mitochondria in MI + Veh compared with Sham + Veh mice was also observed. The wet weight and cross-sectional area of slow muscle fibres (higher XO-derived ROS) was reduced via the down-regulation of protein synthesis-associated mTOR-p70S6K signalling in MI + Veh compared with Sham + Veh mice. These impairments were ameliorated in MI + Feb mice, in association with a reduction of XO-derived ROS production, without affecting cardiac function.
  
  
  
  
  
  XO inhibition during the acute phase post-MI can prevent skeletal muscle abnormalities and exercise intolerance in mice with HF.
  
  
  
• Brain-Derived Neurotrophic Factor Improves Impaired Fatty Acid Oxidation Via the Activation of Adenosine Monophosphate-Activated Protein Kinase-ɑ – Proliferator-Activated Receptor-r Coactivator-1ɑ Signaling in Skeletal Muscle of Mice With Heart Failure
  Junichi Matsumoto; Shingo Takada; Takaaki Furihata; Hideo Nambu; Naoya Kakutani; Satoshi Maekawa; Wataru Mizushima; Ippei Nakano; Arata Fukushima; Takashi Yokota; Shinya Tanaka; Haruka Handa; Hisataka Sabe; Shintaro Kinugawa
  Circulation: Heart Failure, 14, 1, e005890, Ovid Technologies (Wolters Kluwer Health), Jan. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal,
  
  We recently reported that treatment with rhBDNF (recombinant human brain-derived neurotrophic factor) improved the reduced exercise capacity of mice with heart failure (HF) after myocardial infarction (MI). Since BDNF is reported to enhance fatty acid oxidation, we herein conducted an in vivo investigation to determine whether the improvement in exercise capacity is due to the enhancement of the fatty acid oxidation of skeletal muscle via the AMPKα-PGC1α (adenosine monophosphate-activated protein kinase-ɑ–proliferator-activated receptor-r coactivator-1ɑ) axis.
  
  
  
  
  
  MI and sham operations were conducted in C57BL/6J mice. Two weeks postsurgery, we randomly divided the MI mice into groups treated with rhBDNF or vehicle for 2 weeks. AMPKα-PGC1α signaling and mitochondrial content in the skeletal muscle of the mice were evaluated by Western blotting and transmission electron microscopy. Fatty acid β-oxidation was examined by high-resolution respirometry using permeabilized muscle fiber. BDNF-knockout mice were treated with 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside, an activator of AMPK.
  
  
  
  
  
  The rhBDNF treatment significantly increased the expressions of phosphorylated AMPKα and PGC1α protein and the intermyofibrillar mitochondrial density in the MI mice. The lowered skeletal muscle mitochondrial fatty acid oxidation was significantly improved in the rhBDNF-treated MI mice. The reduced exercise capacity and mitochondrial dysfunction of the BDNF-knockout mice were improved by 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside.
  
  
  
  
  
  Beneficial effects of BDNF on the exercise capacity of mice with HF are mediated through an enhancement of fatty acid oxidation via the activation of AMPKα-PGC1α in skeletal muscle. BDNF may become a therapeutic option to improve exercise capacity as an alternative or adjunct to exercise training.
  
  
  
• Type 2 diabetes is an independent predictor of lowered peak aerobic capacity in heart failure patients with non-reduced or reduced left ventricular ejection fraction
  Takahiro Abe; Takashi Yokota; Arata Fukushima; Naoya Kakutani; Takashi Katayama; Ryosuke Shirakawa; Satoshi Maekawa; Hideo Nambu; Yoshikuni Obata; Katsuma Yamanashi; Ippei Nakano; Shingo Takada; Isao Yokota; Koichi Okita; Shintaro Kinugawa; Toshihisa Anzai
  Cardiovascular Diabetology, 19, 1, 142, 142, Springer Science and Business Media LLC, Dec. 2020, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal,
  
  
  Although type 2 diabetes mellitus (T2DM) is one of the most frequent comorbidities in patients with chronic heart failure (CHF), the effects of T2DM on the exercise capacity of CHF patients are fully unknown. Here, we tested the hypothesis that the coexistence of T2DM lowers CHF patients’ peak aerobic capacity.
  
  
  
  
  
  We retrospectively analyzed the cases of 275 Japanese CHF patients with non-reduced ejection fraction (left ventricular ejection fraction [LVEF] ≥ 40%) or reduced EF (LVEF < 40%) who underwent cardiopulmonary exercise testing. We divided them into diabetic and nondiabetic groups in each CHF cohort.
  
  
  
  
  
  The mean peak oxygen uptake (VO₂) value was 16.87 mL/kg/min in the non-reduced LVEF cohort and 15.52 mL/kg/min in the reduced LVEF cohort. The peak VO₂ was lower in the diabetics versus the nondiabetics in the non-reduced LVEF cohort with the mean difference (95% confidence interval [95% CI]) of − 0.93 (− 1.82 to − 0.04) mL/kg/min and in the reduced LVEF cohort with the mean difference of − 1.05 (− 1.96 to − 0.15) mL/kg/min, after adjustment for age-squared, gender, anemia, renal function, LVEF, and log B-type natriuretic peptide (BNP). The adjusted VO₂ at anaerobic threshold (AT), a submaximal aerobic capacity, was also decreased in the diabetic patients with both non-reduced and reduced LVEFs. Intriguingly, the diabetic patients had a lower adjusted peak O₂ pulse than the nondiabetic patients in the reduced LVEF cohort, but not in the non-reduced LVEF cohort. A multivariate analysis showed that the presence of T2DM was an independent predictor of lowered peak VO₂ in CHF patients with non-reduced LVEF and those with reduced LVEF.
  
  
  
  
  
  T2DM was associated with lowered peak VO₂ in CHF patients with non-reduced or reduced LVEF. The presence of T2DM has a negative impact on CHF patients’ exercise capacity, and the degree of impact is partly dependent on their LV systolic function.
  
  
  
• Activation of invariant natural killer T cells by alpha-galactosylceramide ameliorates doxorubicin-induced cardiotoxicity in mice
  Yoshikuni Obata; Naoki Ishimori; Akimichi Saito; Shintaro Kinugawa; Takashi Yokota; Shingo Takada; Ippei Nakano; Naoya Kakutani; Katsuma Yamanashi; Toshihisa Anzai
  European Journal of Preventive Cardiology, 27, 19, 2358, 2361, Oxford University Press (OUP), Dec. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• BDNF as a novel therapeutic candidate for Kennedy's disease
  Takashi Yokota
  Journal of Physiology, 598, 13, 2543, 2544, Wiley, Jul. 2020, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author], [International Magazine]
  English, Scientific journal
• Loop diuretic use is associated with skeletal muscle wasting in patients with heart failure
  Nakano I, Tsuda M, Kinugawa S, Fukushima A, Kakutani N, Takada S, Yokota T
  Journal of Cardiology, 76, 1, 109, 114, Jul. 2020, [Peer-reviewed], [Last author], [Domestic magazines]
  English, Scientific journal, BACKGROUND: Loop diuretics are widely used for the management of fluid retention in patients with heart failure (HF). Sarcopenia, defined as decreased skeletal muscle mass, is frequently present in patients with HF and is associated with poor prognosis. The effects of loop diuretics on skeletal muscle in HF patients have not been fully elucidated. Here, we investigated the impact of loop diuretics on the skeletal muscle mass in patients with HF. METHODS: We conducted a subanalysis of a cross-sectional study from 10 hospitals evaluating 155 patients with HF (age 67 ± 13 yrs, 69% men). RESULTS: We compared the HF patients who were treated with loop diuretics (n = 120) with the patients who were not (n = 35). The thigh and arm circumferences were significantly small in the group treated with loop diuretics compared to those not so treated (39.9 ± 4.8 vs. 43.5 ± 6.9 cm, p < 0.001 and 26.7 ± 3.5 vs. 28.9 ± 6.2 cm, p < 0.001, respectively). In a univariate analysis, higher age, lower body mass index, lower hemoglobin, and loop diuretic use were significantly associated with smaller thigh circumference. In a multivariable analysis, the use of loop diuretics was independently associated with smaller thigh circumference (β = -0.51, 95% confidence interval -0.98 to -0.046, p = 0.032). CONCLUSION: Loop diuretics are associated with decreased thigh and arm circumferences in patients with HF, independent of the severity of HF. Our findings revealed for the first time the adverse effects of loop diuretics on skeletal muscle wasting. These findings will have a significant impact in clinical practice regarding the frequent use of loop diuretics in HF patients.
• Validation of Gene Therapy for Mutant Mitochondria by Delivering Mitochondrial RNA Using a MITO-Porter.
  Eriko Kawamura; Minako Maruyama; Jiro Abe; Akira Sudo; Atsuhito Takeda; Shingo Takada; Takashi Yokota; Shintaro Kinugawa; Hideyoshi Harashima; Yuma Yamada
  Molecular therapy. Nucleic acids, 20, 687, 698, 05 Jun. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Here, we report on validating a mitochondrial gene therapy by delivering nucleic acids to mitochondria of diseased cells by a MITO-Porter, a liposome-based carrier for mitochondrial delivery. We used cells derived from a patient with a mitochondrial disease with a G625A heteroplasmic mutation in the tRNAPhe of the mitochondrial DNA (mtDNA). It has been reported that some mitochondrial gene diseases are caused by heteroplasmic mutations, in which both mutated and wild-type (WT) genes are present, and the accumulation of pathological mutations leads to serious, intractable, multi-organ diseases. Therefore, the decrease of the mutated gene rate is considered to be a useful gene therapy strategy. To accomplish this, wild-type mitochondrial pre-tRNAPhe (pre-WT-tRNAPhe), prepared by in vitro transcription, was encapsulated in the MITO-Porter. The pre-WT-tRNAPhe encapsulated in the MITO-Porter was transfected into diseased mitochondrial cells, and the resulting mutant levels were examined by an amplification refractory mutation system (ARMS)-quantitative PCR. The mutation rate of tRNAPhe was decreased, and this therapeutic effect was sustained even on the 8th day after transfection. Furthermore, mitochondrial respiratory activity of the disease cells was increased after the transfection of therapeutic pre-WT-tRNAPhe. These results support the conclusion that the mitochondrial delivery of therapeutic nucleic acids represents a viable strategy for mitochondrial gene therapy.
• Branched-chain amino acid supplementation ameliorates angiotensin II-induced skeletal muscle atrophy
  Katsuma Yamanashi; Shintaro Kinugawa; Arata Fukushima; Naoya Kakutani; Shingo Takada; Yoshikuni Obata; Ippei Nakano; Takashi Yokota; Yasuyuki Kitaura; Yoshiharu Shimomura; Toshihisa Anzai
  Life Sciences, 250, 117593, 117593, Elsevier BV, Jun. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Angiotensin-converting-enzyme inhibitor prevents skeletal muscle fibrosis in myocardial infarction mice
  Naoya Kakutani; Shingo Takada; Hideo Nambu; Junichi Matsumoto; Takaaki Furihata; Takashi Yokota; Arata Fukushima; Shintaro Kinugawa
  Skeletal Muscle, 10, 1, 11, Springer Science and Business Media LLC, 25 Apr. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Abstract
  
  Background
  
  Transforming growth factor beta (TGF-β)-Smad2/3 is the major signaling pathway of fibrosis, which is characterized by the excessive production and accumulation of extracellular matrix (ECM) components, including collagen. Although the ECM is an essential component of skeletal muscle, fibrosis may be harmful to muscle function. On the other hand, our previous studies have shown that levels of angiotensin II, which acts upstream of TGF-β-Smad2/3 signaling, is increased in mice with myocardial infarction (MI). In this study, we found higher skeletal muscle fibrosis in MI mice compared with control mice, and we investigated the mechanisms involved therein. Moreover, we administered an inhibitor based on the above mechanism and investigated its preventive effects on skeletal muscle fibrosis.
  
  Methods
  
  Male C57BL/6 J mice with MI were created, and sham-operated mice were used as controls. The time course of skeletal muscle fibrosis post-MI was analyzed by picrosirius-red staining (days 1, 3, 7, and 14). Mice were then divided into 3 groups: sham + vehicle (Sham + Veh), MI + Veh, and MI + lisinopril (an angiotensin-converting enzyme [ACE] inhibitor, 20 mg/kg body weight/day in drinking water; MI + Lis). Lis or Veh was administered from immediately after the surgery to 14 days postsurgery.
  
  Results
  
  Skeletal muscle fibrosis was significantly increased in MI mice compared with sham mice from 3 to 14 days postsurgery. Although mortality was lower in the MI + Lis mice than the MI + Veh mice, there was no difference in cardiac function between the 2 groups at 14 days. Skeletal muscle fibrosis and hydroxyproline (a key marker of collagen content) were significantly increased in MI + Veh mice compared with the Sham + Veh mice. Consistent with these results, protein expression of TGF-β and phosphorylated Smad2/3 in the skeletal muscle during the early time points after surgery (days 1–7 postsurgery) and blood angiotensin II at 14 days postsurgery was increased in MI mice compared with sham mice. These impairments were improved in MI + Lis mice, without any effects on spontaneous physical activity, muscle strength, muscle weight, and blood pressure.
  
  Conclusions
  
  ACE inhibitor administration prevents increased skeletal muscle fibrosis during the early phase after MI. Our findings indicate a new therapeutic target for ameliorating skeletal muscle abnormalities in heart diseases.
• Correlation between increased atrial expression of genes related to fatty acid metabolism and autophagy in patients with chronic atrial fibrillation
  Yasushige Shingu; Shingo Takada; Takashi Yokota; Ryosuke Shirakawa; Akira Yamada; Tomonori Ooka; Hiroki Katoh; Suguru Kubota; Yoshiro Matsui
  PLoS One, 15, 4, e0224713, 21 Apr. 2020, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, Atrial metabolic disturbance contributes to the onset and development of atrial fibrillation (AF). Autophagy plays a role in maintaining the cellular energy balance. We examined whether atrial gene expressions related to fatty acid metabolism and autophagy are altered in chronic AF and whether they are related to each other. Right atrial tissue was obtained during heart surgery from 51 patients with sinus rhythm (SR, n = 38) or chronic AF (n = 13). Preoperative fasting serum free-fatty-acid levels were significantly higher in the AF patients. The atrial gene expression of fatty acid binding protein 3 (FABP3), which is involved in the cells' fatty acid uptake and intracellular fatty acid transport, was significantly increased in AF patients compared to SR patients; in the SR patients it was positively correlated with the right atrial diameter and intra-atrial electromechanical delay (EMD), parameters of structural and electrical atrial remodeling that were evaluated by an echocardiography. In contrast, the two groups' atrial contents of diacylglycerol (DAG), a toxic fatty acid metabolite, were comparable. Importantly, the atrial gene expression of microtubule-associated protein light chain 3 (LC3) was significantly increased in AF patients, and autophagy-related genes including LC3 were positively correlated with the atrial expression of FABP3. In conclusion, in chronic AF patients, the atrial expression of FABP3 was upregulated in association with autophagy-related genes without altered atrial DAG content. Our findings may support the hypothesis that dysregulated cardiac fatty acid metabolism contributes to the progression of AF and induction of autophagy has a cardioprotective effect against cardiac lipotoxicity in chronic AF.
• Mitochondrial respiration of complex II is not lower than that of complex I in mouse skeletal muscle
  Satoshi Maekawa; Shingo Takada; Takaaki Furihata; Arata Fukushima; Takashi Yokota; Shintaro Kinugawa
  Biochemistry and Biophysics Reports, 21, 100717, 100717, Elsevier BV, Mar. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Serum Brain-Derived Neurotrophic Factor Levels Are Associated with Skeletal Muscle Function but Not with Muscle Mass in Patients with Heart Failure
  Ippei Nakano; Shintaro Kinugawa; Hiroaki Hori; Arata Fukushima; Takashi Yokota; Shingo Takada; Naoya Kakutani; Yoshikuni Obata; Katsuma Yamanashi; Toshihisa Anzai
  International Heart Journal, 61, 1, 96, 102, 31 Jan. 2020, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, Heart failure (HF) is associated with aberrant skeletal muscle impairments, which are closely linked to the severity of HF. A low level of brain-derived neurotrophic factor (BDNF), a myokine produced in the skeletal muscle, is known to be involved in reduced exercise capacity and poor prognosis in HF. However, little is known about the factors or conditions of skeletal muscle associated with BDNF levels. We investigated the association between serum BDNF levels and the skeletal muscle mass and function in HF patients (n = 60, 63 ± 13 years) and age-matched controls (n = 29, 61 ± 16 years). The serum BDNF level was significantly lower in the HF patients compared to the controls (24.9 ± 0.9 versus 28.6 ± 1.3, P = 0.021). In a univariate analysis, BDNF was significantly correlated with the peak oxygen uptake, estimated glomerular filtration rate, 10-m gait speed, and muscle strength, but not with the body mass index or lean mass in the HF group. A multiple linear regression analysis revealed that BDNF was independently associated with muscle strength (β-coefficient = 2.80, 95%CI: 1.89-11.8, P = 0.008). Serum BDNF levels were associated with exercise capacity and skeletal muscle function, but not with muscle mass. These novel findings may suggest that BDNF production is controlled by muscle function and activity and consequently regulates exercise capacity, highlighting the importance of adequate training regarding skeletal muscle in HF patients.
• Empagliflozin restores lowered exercise endurance capacity via the activation of skeletal muscle fatty acid oxidation in a murine model of heart failure
  Hideo Nambu; Shingo Takada; Arata Fukushima; Junichi Matsumoto; Naoya Kakutani; Satoshi Maekawa; Ryosuke Shirakawa; Ippei Nakano; Takaaki Furihata; Takashi Katayama; Katsuma Yamanashi; Yoshikuni Obata; Akimichi Saito; Takashi Yokota; Shintaro Kinugawa
  European Journal of Pharmacology, 866, 172810, 172810, 05 Jan. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Decreased exercise capacity, which is an independent predictor of the poor prognosis of patients with heart failure (HF), is attributed to markedly impaired skeletal muscle mitochondrial function and fatty acid oxidation. Previous studies reported that the administration of an inhibitor of sodium-glucose cotransporter 2 (SGLT2) increases ketone body production and fat utilization in type 2 diabetic mice. In this study, we investigated the effects of SGLT2 inhibitor administration on exercise endurance and skeletal muscle mitochondrial function with fatty acid oxidation in a murine model of HF after the induction of myocardial infarction (MI). Two weeks post-MI, HF mice were divided into 2 groups, i.e., with or without treatment with the SGLT2 inhibitor empagliflozin (Empa, 300 mg/kg of food). Consistent with previous studies, urinary glucose and blood beta-hydroxybutyrate levels were increased in the HF+Empa mice compared with the sham and HF mice 4 weeks after the start of Empa administration. Exercise endurance capacity was limited in the HF mice but was ameliorated in the HF+Empa mice, without any effects on cardiac function, food intake, spontaneous physical activity, skeletal muscle strength, and skeletal muscle weight. Mitochondrial oxidative phosphorylation capacity with fatty acid substrates was reduced in the skeletal muscle of HF mice, and this decrease was ameliorated in the HF+Empa mice. Our results demonstrate that SGLT2 inhibitors may be novel therapeutics against reduced exercise endurance capacity in HF, by improving mitochondrial fatty acid oxidation in skeletal muscle.
• A mitochondrial delivery system using liposome-based nanocarriers that target myoblast cells.
  Takashi Katayama; Shintaro Kinugawa; Shingo Takada; Takaaki Furihata; Arata Fukushima; Takashi Yokota; Toshihisa Anzai; Mitsue Hibino; Hideyoshi Harashima; Yuma Yamada
  Mitochondrion, 49, 66, 72, Nov. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Mitochondrial function is reduced in skeletal muscles of many patients with systemic diseases and it is difficult to deliver medicinal substances to mitochondria in such tissue. In this study, we report on attempts to develop liposome-based carriers for mitochondrial delivery using mouse myoblasts (C2C12) by varying the lipid composition of the carriers. We found that a liposome that contains an optimal lipid modified with the KALA peptide (a cellular uptake and mitochondrial targeting device) was the most effective nanocarrier for achieving mitochondrial delivery in C2C12 cells. We also report on successful mitochondrial transgene expression using the carriers encapsulating a mitochondrial DNA vector as we previously reported.
• Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients
  Ryosuke Shirakawa; Takashi Yokota; Takayuki Nakajima; Shingo Takada; Miwako Yamane; Takaaki Furihata; Satoshi Maekawa; Hideo Nambu; Takashi Katayama; Arata Fukushima; Akimichi Saito; Naoki Ishimori; Flemming Dela; Shintaro Kinugawa; Toshihisa Anzai
  Scientific Reports, 9, 1, 14709, 14709, 11 Oct. 2019, [Peer-reviewed], [Corresponding author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, Systemic oxidative stress plays a key role in the development of chronic heart failure (CHF). We tested the hypothesis that mitochondrial reactive oxygen species (ROS) generation in circulating peripheral blood mononuclear cells (PBMCs) contributes to CHF progression. A total of 31 patients who had a history of hospital admission due to worsening HF were enrolled and grouped as having either mild CHF defined as New York Heart Association (NYHA) functional class I-II or moderate-to-severe CHF defined as NYHA functional class III. ROS levels in PBMC mitochondria were significantly increased in CHF patients with NYHA functional class III compared to those with NYHA functional class I-II, accompanied by impaired mitochondrial respiratory capacity in PBMCs. ROS generation in PBMC mitochondria was positively correlated with urinary 8-hydroxydeoxyguanosine, a systemic oxidative stress marker, in CHF patients. Importantly, mitochondrial ROS generation in PBMCs was directly correlated with plasma levels of B-type natriuretic peptide, a biomarker for severity of HF, and inversely correlated with peak oxygen uptake, a parameter of exercise capacity, in CHF patients. The study showed that ROS generation in PBMC mitochondria was higher in patients with advanced CHF, and it was associated with disease severity and exercise intolerance in CHF patients.
• Enhanced Echo Intensity of Skeletal Muscle Is Associated With Exercise Intolerance in Patients With Heart Failure
  Ippei Nakano; Hiroaki Hori; Arata Fukushima; Takashi Yokota; Shintaro Kinugawa; Shingo Takada; Katsuma Yamanashi; Yoshikuni Obata; Yasuyuki Kitaura; Naoya Kakutani; Takahiro Abe; Toshihisa Anzai
  Journal of Cardiac Failure, 26, 8, 685, 693, 15 Sep. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: Skeletal muscle is quantitatively and qualitatively impaired in patients with heart failure (HF), which is closely linked to lowered exercise capacity. Ultrasonography (US) for skeletal muscle has emerged as a useful, noninvasive tool to evaluate muscle quality and quantity. Here we investigated whether muscle quality based on US-derived echo intensity (EI) is associated with exercise capacity in patients with HF. METHODS AND RESULTS: Fifty-eight patients with HF (61 ± 12 years) and 28 control subjects (58 ± 14 years) were studied. The quadriceps femoris echo intensity (QEI) was significantly higher and the quadriceps femoris muscle thickness (QMT) was significantly lower in the patients with HF than the controls (88.3 ± 13.4 vs 81.1 ± 7.5, P= .010; 5.21 ± 1.10 vs 6.54 ±1.34 cm, P< .001, respectively). By univariate analysis, QEI was significantly correlated with age, peak oxygen uptake (VO2), and New York Heart Association class in the HF group. A multivariable analysis revealed that the QEI was independently associated with peak VO2 after adjustment for age, gender, body mass index, and QMT: β-coefficient = -11.80, 95%CI (-20.73, -2.86), P= .011. CONCLUSION: Enhanced EI in skeletal muscle was independently associated with lowered exercise capacity in HF. The measurement of EI is low-cost, easily accessible, and suitable for assessment of HF-related alterations in skeletal muscle quality.
• Resistance training with interval blood flow restriction effectively enhances intramuscular metabolic stress with less ischemic duration and discomfort
  Koichi Okita; Shingo Takada; Noriteru Morita; Masashige Takahashi; Kagami Hirabayashi; Takashi Yokota; Shintaro Kinugawa
  Applied Physiology, Nutrition, and Metabolism, 44, 7, 759, 764, Canadian Science Publishing, Jul. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Increases in muscle size and strength similar to those obtained with high resistance load can be achieved by combining lower loads with continuous blood flow restriction (BFR). However, high ratings for distress have been reported for continuous BFR. Therefore, we investigated the efficacy (metabolic stress) of BFR applied only during intervals in resistance exercise. Seven healthy men performed three 1-min sets of plantar flexion (30 reps/min) with 1-min rest intervals under 4 conditions: low-load resistance exercise (L, 20% 1-repetition maximum (1RM)) without BFR (L-noBFR), L with BFR during exercise sets (L-exBFR), L with BFR during rest intervals (L-intBFR), and L with continuous BFR during both exercise and rest intervals (L-conBFR). Based on the results of the first experiment, we performed additional protocols using a moderate load (M, 40% 1RM) with intermittent (exercise or rest intervals) BFR (M-exBFR and M-intBFR). Intramuscular metabolic stress, defined as decreases in phosphocreatine and intramuscular pH, was evaluated by ³¹P magnetic resonance spectroscopy. Rated perceived exertion (RPE) was also assessed. At the end of exercise, total decreases in phosphocreatine and intramuscular pH were similar among L-noBFR, L-intBFR, and L-exBFR and significantly less than those in L-conBFR (p < 0.05). In contrast, changes in these variables in M-intBFR but not in M-exBFR were similar to those in L-conBFR. Nevertheless, RPE was lower in M-intBFR than in both M-exBFR and L-conBFR (p < 0.05). The effect of intermittent BFR during exercise might be insufficient to induce metabolic stress when using a low load. However, effective metabolic stress for muscle adaptation could be obtained by moderate-load resistance exercise with BFR during intervals with less ischemic duration and discomfort.
• Impact of admission liver stiffness on long-term clinical outcomes in patients with acute decompensated heart failure
  Kazunori Omote; Toshiyuki Nagai; Naoya Asakawa; Kiwamu Kamiya; Yusuke Tokuda; Tadao Aikawa; Arata Fukushima; Keiji Noguchi; Yoshiya Kato; Hirokazu Komoriyama; Mutsumi Nishida; Yusuke Kudo; Hiroyuki Iwano; Takashi Yokota; Toshihisa Anzai
  Heart and Vessels, 34, 6, 984, 991, Springer Science and Business Media LLC, Jun. 2019, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal
• Clinical Impact and Associated Factors of Delayed Ambulation in Patients With Acute Heart Failure
  Koji Ishikawa; Arata Fukushima; Takashi Yokota; Shingo Takada; Takaaki Furihata; Naoya Kakutani; Katsuma Yamanashi; Yoshikuni Obata; Ippei Nakano; Takahiro Abe; Shintaro Kinugawa; Toshihisa Anzai
  Circulation Reports, 1, 4, 179, 186, Japanese Circulation Society, 10 Apr. 2019, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, Background: In heart failure (HF) management, early ambulation is recommended to prevent physical deconditioning. The effects of delayed ambulation on later clinical outcomes and the factors linked to delayed ambulation in hospitalized HF patients, however, remain unestablished. Methods and Results: We retrospectively investigated 101 patients (mean age, 66±17 years) who were hospitalized for acute decompensated HF. During the mean follow-up of 244±15 days after hospital discharge, 34 patients had cardiovascular events leading to death or unplanned readmission. Patients with cardiovascular events had longer median days to acquire ambulation than those without cardiovascular events (11 days, IQR, 8-20 days vs. 7 days, IQR, 5-15 days, P<0.001). The optimal cut-off period until initiation of ambulation to discriminate cardiovascular events was 8 days, indicating that longer days (≥8 days) to acquire ambulation was associated with higher rates of cardiovascular events, even after adjustment of multiple confounders. On multivariate analysis, age >65 years (odds ratio [OR], 2.49; 95% confidence interval [CI]: 1.04-6.09) and increase in blood urea nitrogen (BUN; OR, 1.04; 95% CI: 1.01-1.08) were independent predictors of delayed ambulation. Conclusions: Delayed ambulation is associated with older age and increased BUN in patients with acute HF. Time to ambulation in the recovery phase of acute HF is important, and delayed ambulation may increase the rate of cardiovascular events after hospital discharge.
• Diastolic Intra-Left Ventricular Pressure Difference During Exercise: Strong Determinant and Predictor of Exercise Capacity in Patients With Heart Failure.
  Shingo Tsujinaga; Hiroyuki Iwano; Miwa Sarashina; Taichi Hayashi; Michito Murayama; Ayako Ichikawa; Masahiro Nakabachi; Hisao Nishino; Shinobu Yokoyama; Arata Fukushima; Takashi Yokota; Kazunori Okada; Sanae Kaga; Pavlos P Vlachos; Toshihisa Anzai
  Journal of Cardiac Failure, 25, 4, 268, 277, Apr. 2019, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, BACKGROUND: Although the enhancement of early-diastolic intra-left ventricular pressure difference (IVPD) during exercise is considered to maintain exercise capacity, little is known about their relationship in heart failure (HF). METHODS AND RESULTS: Cardiopulmonary exercise testing and exercise-stress echocardiography were performed in 50 HF patients (left ventricular [LV] ejection fraction 39 ± 15%). Echocardiographic images were obtained at rest and submaximal and peak exercise. Color M-mode Doppler images of LV inflow were used to determine IVPD. Thirty-five patients had preserved exercise capacity (peak oxygen consumption [VO2] ≥14 mL·kg-1·min-1; group 1) and 15 patients had reduced exercise capacity (group 2). During exercise, IVPD increased only in group 1 (group 1: 1.9 ± 0.9 mm Hg at rest, 4.1 ± 2.0 mm Hg at submaximum, 4.7 ± 2.1 mm Hg at peak; group 2: 1.9 ± 0.8 mm Hg at rest, 2.1 ± 0.9 mm Hg at submaximum, 2.1 ± 0.9 mm Hg at peak). Submaximal IVPD (r = 0.54) and peak IVPD (r = 0.69) were significantly correlated with peak VO2. Peak IVPD determined peak VO2 independently of LV ejection fraction. Moreover, submaximal IVPD could well predict the reduced exercise capacity. CONCLUSION: Early-diastolic IVPD during exercise was closely associated with exercise capacity in HF. In addition, submaximal IVPD could be a useful predictor of exercise capacity without peak exercise in HF patients.
• Progressive Mobilization Program for Patients With Acute Heart Failure Reduces Hospital Stay and Improves Clinical Outcome
  Naoya Kakutani; Arata Fukushima; Shintaro Kinugawa; Takashi Yokota; Tatsuya Oikawa; Mikito Nishikawa; Risako Nakamura; Takanori Tsukada; Shigeki Mori; Ichiro Yoshida; Toshihisa Anzai
  Circulation Reports, 1, 3, 123, 130, Japanese Circulation Society, 08 Mar. 2019, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, Background: Early ambulation has been shown to be associated with shorter hospital stay and better clinical outcomes in patients with acute heart failure (HF). Early mobilization program in combination with structured exercise training is recommended, but has yet to be developed and implemented in HF. Methods and Results: We developed a progressive mobilization program for HF patients that classifies the mobilization process into 7 stages based on disease condition and physical function. We retrospectively analyzed 136 patients with acute HF (80±11 years), who were assigned either to the mobilization program (intervention group, n=75) or to usual care (control group, n=61). The program was safely implemented without any adverse events. Hospital stay was significantly reduced in the intervention group compared with the control group (33±25 vs. 51±36 days, P<0.01). The intervention group had higher activities of daily living (ADL) score at discharge evaluated using the Barthel index (64±38 vs. 49±36, P<0.05). The intervention group also had a higher percentage of discharge to home (71% vs. 52%, P<0.05) and a lower rate of HF-related readmission (16% vs. 36%, P<0.05) compared with the control group. Conclusions: The progressive mobilization program for acute HF was feasible and was associated with better ADL and reduced hospital stay, leading to improvement of clinical outcome.
• Impaired mitochondrial oxidative phosphorylation capacity in epicardial adipose tissue is associated with decreased concentration of adiponectin and severity of coronary atherosclerosis.
  Takayuki Nakajima; Takashi Yokota; Yasushige Shingu; Akira Yamada; Yutaka Iba; Kosuke Ujihira; Satoru Wakasa; Tomonori Ooka; Shingo Takada; Ryosuke Shirakawa; Takashi Katayama; Takaaki Furihata; Arata Fukushima; Ryosuke Matsuoka; Hiroshi Nishihara; Flemming Dela; Katsuhiko Nakanishi; Yoshiro Matsui; Shintaro Kinugawa
  Scientific Reports, 9, 1, 3535, 3535, 05 Mar. 2019, [Peer-reviewed], [Corresponding author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal, Epicardial adipose tissue (EAT), a source of adipokines, is metabolically active, but the role of EAT mitochondria in coronary artery disease (CAD) has not been established. We investigated the association between EAT mitochondrial respiratory capacity, adiponectin concentration in the EAT, and coronary atherosclerosis. EAT samples were obtained from 25 patients who underwent elective cardiac surgery. Based on the coronary angiographycal findings, the patients were divided into two groups; coronary artery disease (CAD; n = 14) and non-CAD (n = 11) groups. The mitochondrial respiratory capacities including oxidative phosphorylation (OXPHOS) capacity with non-fatty acid (complex I and complex I + II-linked) substrates and fatty acids in the EAT were significantly lowered in CAD patients. The EAT mitochondrial OXPHOS capacities had a close and inverse correlation with the severity of coronary artery stenosis evaluated by the Gensini score. Intriguingly, the protein level of adiponectin, an anti-atherogenic adipokine, in the EAT was significantly reduced in CAD patients, and it was positively correlated with the mitochondrial OXPHOS capacities in the EAT and inversely correlated with the Gensini score. Our study showed that impaired mitochondrial OXPHOS capacity in the EAT was closely linked to decreased concentration of adiponectin in the EAT and severity of coronary atherosclerosis.
• Brain-Derived Neurotrophic Factor Improves Limited Exercise Capacity in Mice With Heart Failure.
  Junichi Matsumoto; Shingo Takada; Shintaro Kinugawa; Takaaki Furihata; Hideo Nambu; Naoya Kakutani; Masaya Tsuda; Arata Fukushima; Takashi Yokota; Shinya Tanaka; Hidehisa Takahashi; Masashi Watanabe; Shigetsugu Hatakeyama; Masaki Matsumoto; Keiichi I Nakayama; Yutaro Otsuka; Hisataka Sabe; Hiroyuki Tsutsui; Toshihisa Anzai
  Circulation, 138, 18, 2064, 2066, 30 Oct. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Impact of High Respiratory Exchange Ratio During Submaximal Exercise on Adverse Clinical Outcome in Heart Failure.
  Naoya Kakutani; Arata Fukushima; Takashi Yokota; Takashi Katayama; Hideo Nambu; Ryosuke Shirakawa; Satoshi Maekawa; Takahiro Abe; Shingo Takada; Takaaki Furihata; Kota Ono; Koichi Okita; Shintaro Kinugawa; Toshihisa Anzai
  Circulation Journal, 82, 11, 2753, 2760, 25 Oct. 2018, [Peer-reviewed], [Corresponding author], [Domestic magazines]
  English, Scientific journal, BACKGROUND: Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown. Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I-III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2 had an inverse correlation with RER at AT workload (r=-0.256), but not at rest (r=-0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER (<0.97) groups. Patients with high RER at AT workload were characterized by older age, lower body mass index, anemia, and advanced NYHA class. After propensity score matching, peak V̇O2 tended to be lower in the high-RER than in the low-RER group (14.9±4.5 vs. 16.1±5.0 mL/kg/min, P=0.06). On Kaplan-Meier analysis, HF patients with a high RER at AT workload had significantly worse clinical outcomes, including all-cause mortality and rate of readmission due to HF worsening over 3 years (29% vs. 15%, P=0.01). CONCLUSIONS: High RER during submaximal exercise, particularly at AT workload, is associated with poor clinical outcome in HF patients.
• Protein acetylation in skeletal muscle mitochondria is involved in impaired fatty acid oxidation and exercise intolerance in heart failure
  Masaya Tsuda; Arata Fukushima; Junichi Matsumoto; Shingo Takada; Naoya Kakutani; Hideo Nambu; Katsuma Yamanashi; Takaaki Furihata; Takashi Yokota; Koichi Okita; Shintaro Kinugawa; Toshihisa Anzai
  Journal of Cachexia, Sarcopenia and Muscle, 9, 5, 844, 859, Oct. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: Exercise intolerance is a common clinical feature and is linked to poor prognosis in patients with heart failure (HF). Skeletal muscle dysfunction, including impaired energy metabolism in the skeletal muscle, is suspected to play a central role in this intolerance, but the underlying mechanisms remain elusive. Lysine acetylation, a recently identified post-translational modification, has emerged as a major contributor to the derangement of mitochondrial metabolism. We thus investigated whether mitochondrial protein acetylation is associated with impaired skeletal muscle metabolism and lowered exercise capacity in both basic and clinical settings of HF. METHODS: We first conducted a global metabolomic analysis to determine whether plasma acetyl-lysine is a determinant factor for peak oxygen uptake (peak VO2 ) in HF patients. We then created a murine model of HF (n = 11) or sham-operated (n = 11) mice with or without limited exercise capacity by ligating a coronary artery, and we tested the gastrocnemius tissues by using mass spectrometry-based acetylomics. A causative relationship between acetylation and the activity of a metabolic enzyme was confirmed in in vitro studies. RESULTS: The metabolomic analysis verified that acetyl-lysine was the most relevant metabolite that was negatively correlated with peak VO2 (r = -0.81, P < 0.01). At 4 weeks post-myocardial infarction HF, a treadmill test showed lowered work (distance × body weight) and peak VO2 in the HF mice compared with the sham-operated mice (11 ± 1 vs. 23 ± 1 J, P < 0.01; 143 ± 5 vs. 159 ± 3 mL/kg/min, P = 0.01; respectively). As noted, the protein acetylation of gastrocnemius mitochondria was 48% greater in the HF mice than the sham-operated mice (P = 0.047). Acetylproteomics identified the mitochondrial enzymes involved in fatty acid β-oxidation (FAO), the tricarboxylic acid cycle, and the electron transport chain as targets of acetylation. In parallel, the FAO enzyme (β-hydroxyacyl CoA dehydrogenase) activity and fatty acid-driven mitochondrial respiration were reduced in the HF mice. This alteration was associated with a decreased expression of mitochondrial deacetylase, Sirtuin 3, because silencing of Sirtuin 3 in cultured skeletal muscle cells resulted in increased mitochondrial acetylation and reduced β-hydroxyacyl CoA dehydrogenase activity. CONCLUSIONS: Enhanced mitochondrial protein acetylation is associated with impaired FAO in skeletal muscle and reduced exercise capacity in HF. Our results indicate that lysine acetylation is a crucial mechanism underlying deranged skeletal muscle metabolism, suggesting that its modulation is a potential approach for exercise intolerance in HF.
• Randomized Trial of Effect of Urate-Lowering Agent Febuxostat in Chronic Heart Failure Patients with Hyperuricemia (LEAF-CHF)
  Takashi Yokota; Arata Fukushima; Shintaro Kinugawa; Takahiro Okumura; Toyoaki Murohara; Hiroyuki Tsutsui
  International Heart Journal, 59, 5, 976, 982, International Heart Journal (Japanese Heart Journal), 01 Sep. 2018, [Peer-reviewed], [Lead author], [Domestic magazines]
  English, Scientific journal, Hyperuricemia is an independent predictor of mortality in patients with chronic heart failure. The aim of the study is to determine whether a urate-lowering agent febuxostat, an inhibitor of xanthine oxidase, may improve the clinical outcomes in chronic heart failure patients with hyperuricemia when compared to conventional treatment. This multicenter, prospective, randomized, open-label, blinded endpoint study with a follow-up period of 24 weeks will enroll 200 Japanese chronic heart failure patients with hyperuricemia. The eligibility criteria include a diagnosis of chronic heart failure (New York Heart Association functional class II-III with a history of hospitalization due to worsening of heart failure within the last 2 years), reduced left ventricular systolic function (left ventricular ejection fraction < 40%) and increased plasma natriuretic peptide [plasma B-type natriuretic peptide (BNP) ≥ 100 pg/mL or N-terminal pro BNP (NT-proBNP) ≥ 400 pg/mL], and hyperuricemia (serum uric acid >7.0 mg/dL and ≤ 10 mg/dL) at the screening visit. The primary outcome is the difference in the plasma BNP levels between the baseline and 24 weeks of treatment. The plasma BNP levels are measured in the central laboratory in a blinded manner. This study investigates the efficacy and safety of febuxostat in chronic heart failure patients with hyperuricemia.
• Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus
  Thomsen K, Yokota T, Hasan-Olive MM, Sherazi N, Fakouri NB, Desler C, Regnell CE, Larsen S, Rasmussen LJ, Dela F, Bergersen LH, Lauritzen M
  Neurobiol Aging, 61, 215, 224, Jan. 2018, [Peer-reviewed], [Lead author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Deletion of NAD(P)H Oxidase 2 Prevents Angiotensin II-Induced Skeletal Muscle Atrophy
  Tomoyasu Kadoguchi; Shingo Takada; Takashi Yokota; Takaaki Furihata; Junichi Matsumoto; Masaya Tsuda; Wataru Mizushima; Arata Fukushima; Koichi Okita; Shintaro Kinugawa
  BioMed Research International, 2018, 1, 10, Wiley, 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Skeletal muscle atrophy is induced by an imbalance between protein synthesis and degradation. Our previous studies reported that angiotensin II (AII) directly induced muscle atrophy in mice. This study investigated the role of NAD(P)H oxidase 2 (Nox2) activation by AII in the induction of skeletal muscle atrophy. For 4 weeks, either saline (vehicle: V) or AII (1000 ng kg⁻¹ min⁻¹) was infused into male wild-type (WT) and Nox2 knockout (KO) mice via osmotic minipumps. Experiments were performed in the following 4 groups: WT + V, KO + V, WT + AII, and KO + AII. Body weight, muscle weight, and myocyte cross-sectional area were significantly decreased in WT + AII compared to WT + V mice, and these changes were not observed in KO + AII mice. Akt phosphorylation of Ser473 and p70S6K of Thr389 was decreased, gene expression levels of MuRF-1 and atrogin-1 were increased in WT + AII compared to WT + V, and these changes were significantly attenuated in KO + AII mice. The deletion of Nox2 prevented AII-induced skeletal muscle atrophy via improving the balance between protein synthesis and degradation. Therefore, Nox2 may be a therapeutic target for AII-induced skeletal muscle atrophy.
• Decreased gene expression of fatty acid binding protein 3 in the atrium of patients with new onset of atrial fibrillation in cardiac perioperative phase
  Yasushige Shingu; Takashi Yokota; Shingo Takada; Haruki Niwano; Tomonori Ooka; Hiroki Katoh; Tsuyoshi Tachibana; Suguru Kubota; Yoshiro Matsui
  Journal of Cardiology, 71, 1, 65, 70, Japanese College of Cardiology (Nippon-Sinzobyo-Gakkai), 01 Jan. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Pre-ischaemic mitochondrial substrate constraint by inhibition of malate-aspartate shuttle preserves mitochondrial function after ischaemia-reperfusion
  Nichlas Riise Jespersen; Takashi Yokota; Nicolaj Brejnholt Støttrup; Andreas Bergdahl; Kim Bolther Pælestik; Jonas Agerlund Povlsen; Flemming Dela; Hans Erik Bøtker
  Journal of Physiology, 595, 12, 3765, 3780, 27 Feb. 2017, [Peer-reviewed], [Corresponding author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome
  Takashi Yokota; Shintaro Kinugawa; Kagami Hirabayashi; Tadashi Suga; Shingo Takada; Masashi Omokawa; Tomoyasu Kadoguchi; Masashige Takahashi; Arata Fukushima; Shouji Matsushima; Mayumi Yamato; Koichi Okita; Hiroyuki Tsutsui
  Journal of Diabetes Investigation, 8, 4, 535, 541, 31 Jan. 2017, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal
• The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes
  Wataru Mizushima; Hidehisa Takahashi; Masashi Watanabe; Shintaro Kinugawa; Shouji Matsushima; Shingo Takada; Takashi Yokota; Takaaki Furihata; Junichi Matsumoto; Masaya Tsuda; Ikuru Chiba; Shun Nagashima; Shigeru Yanagi; Masaki Matsumoto; Keiichi I. Nakayama; Hiroyuki Tsutsui; Shigetsugu Hatakeyama
  Journal of Molecular and Cellular Cardiology, 100, 43, 53, Nov. 2016, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Serum myostatin levels are independently associated with skeletal muscle wasting in patients with heart failure
  Takaaki Furihata; Shintaro Kinugawa; Arata Fukushima; Shingo Takada; Tsuneaki Homma; Yoshihiro Masaki; Takahiro Abe; Takashi Yokota; Koji Oba; Koichi Okita; Hiroyuki Tsutsui
  International Journal of Cardiology, 220, 483, 487, Oct. 2016, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling
  Shouji Matsushima; Junya Kuroda; Peiyong Zhai; Tong Liu; Shohei Ikeda; Narayani Nagarajan; Shin-ichi Oka; Takashi Yokota; Shintaro Kinugawa; Chiao-Po Hsu; Hong Li; Hiroyuki Tsutsui; Junichi Sadoshima
  Journal of Clinical Investigation, 126, 9, 3403, 3416, 15 Aug. 2016, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Dipeptidyl peptidase-4 inhibitor improved exercise capacity and mitochondrial biogenesis in mice with heart failure via activation of glucagon-like peptide-1 receptor signalling
  Shingo Takada; Yoshihiro Masaki; Shintaro Kinugawa; Junichi Matsumoto; Takaaki Furihata; Wataru Mizushima; Tomoyasu Kadoguchi; Arata Fukushima; Tsuneaki Homma; Masashige Takahashi; Shinichi Harashima; Shouji Matsushima; Takashi Yokota; Shinya Tanaka; Koichi Okita; Hiroyuki Tsutsui
  Cardiovascular Research, 111, 4, 338, 347, 21 Jul. 2016, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• The experimental model of transition from compensated cardiac hypertrophy to failure created by transverse aortic constriction in mice
  Takaaki Furihata; Shintaro Kinugawa; Shingo Takada; Arata Fukushima; Masashige Takahashi; Tsuneaki Homma; Yoshihiro Masaki; Masaya Tsuda; Junichi Matsumoto; Wataru Mizushima; Shouji Matsushima; Takashi Yokota; Hiroyuki Tsutsui
  IJC Heart & Vasculature, 11, 24, 28, Elsevier BV, Jun. 2016, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice
  Arata Fukushima; Shintaro Kinugawa; Shingo Takada; Junichi Matsumoto; Takaaki Furihata; Wataru Mizushima; Masaya Tsuda; Takashi Yokota; Shouji Matsushima; Koichi Okita; Hiroyuki Tsutsui
  European Journal of Pharmacology, 779, 147, 156, May 2016, [International Magazine]
  English, Scientific journal
• Low-intensity exercise under ischemic conditions enhances metabolic stress in patients with heart failure
  Masashige Takahashi; Shintaro Kinugawa; Shingo Takada; Kagami Hirabayashi; Takashi Yokota; Shouji Matsushima; Akimichi Saito; Koichi Okita; Hiroyuki Tsutsui
  International Journal of Cardiology, 201, 142, 144, Dec. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Sesamin prevents decline in exercise capacity and impairment of skeletal muscle mitochondrial function in mice with high‐fat diet‐induced diabetes
  Shingo Takada; Shintaro Kinugawa; Shouji Matsushima; Daisuke Takemoto; Takaaki Furihata; Wataru Mizushima; Arata Fukushima; Takashi Yokota; Yoshiko Ono; Hiroshi Shibata; Koichi Okita; Hiroyuki Tsutsui
  Experimental Physiology, 100, 11, 1319, 1330, Oct. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Skeletal muscle mitochondrial H2O2 emission increases with immobilization and decreases after aerobic training in young and older men
  Martin Gram; Andreas Vigelsø; Takashi Yokota; Jørn Wulff Helge; Flemming Dela; Martin Hey‐Mogensen
  Journal of Physiology, 593, 17, 4011, 4027, 27 Jul. 2015, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy
  Liselotte B. Christiansen; Flemming Dela; Jørgen Koch; Christina N. Hansen; Pall S. Leifsson; Takashi Yokota
  American Journal of Physiology-Heart and Circulatory Physiology, 308, 10, H1237, H1247, 15 May 2015, [Peer-reviewed], [Last author, Corresponding author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress
  Mikito Nishikawa; Naoki Ishimori; Shingo Takada; Akimichi Saito; Tomoyasu Kadoguchi; Takaaki Furihata; Arata Fukushima; Shouji Matsushima; Takashi Yokota; Shintaro Kinugawa; Hiroyuki Tsutsui
  Nephrology Dialysis Transplantation, 30, 6, 934, 942, 15 Apr. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Serum Brain-Derived Neurotropic Factor Level Predicts Adverse Clinical Outcomes in Patients With Heart Failure
  Arata Fukushima; Shintaro Kinugawa; Tsuneaki Homma; Yoshihiro Masaki; Takaaki Furihata; Takashi Yokota; Shouji Matsushima; Shingo Takada; Tomoyasu Kadoguchi; Koji Oba; Koichi Okita; Hiroyuki Tsutsui
  Journal of Cardiac Failure, 21, 4, 300, 306, Elsevier BV, Apr. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Angiotensin II can directly induce mitochondrial dysfunction, decrease oxidative fibre number and induce atrophy in mouse hindlimb skeletal muscle
  Tomoyasu Kadoguchi; Shintaro Kinugawa; Shingo Takada; Arata Fukushima; Takaaki Furihata; Tsuneaki Homma; Yoshihiro Masaki; Wataru Mizushima; Mikito Nishikawa; Masashige Takahashi; Takashi Yokota; Shouji Matsushima; Koichi Okita; Hiroyuki Tsutsui
  Experimental Physiology, 100, 3, 312, 322, 12 Feb. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Tissue-specific and substrate-specific mitochondrial bioenergetics in feline cardiac and skeletal muscles
  Liselotte Bruun CHRISTIANSEN; Flemming DELA; Jørgen KOCH; Takashi YOKOTA
  Journal of Veterinary Medical Science, 77, 6, 669, 675, 2015, [Peer-reviewed], [Last author, Corresponding author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Serum choline plasmalogens-those with oleic acid in sn-2-are biomarkers for coronary artery disease
  Megumi Nishimukai; Ryouta Maeba; Akiko Ikuta; Naoya Asakawa; Kiwamu Kamiya; Shiro Yamada; Takashi Yokota; Mamoru Sakakibara; Hiroyuki Tsutsui; Toshihiro Sakurai; Yuji Takahashi; Shu-Ping Hui; Hitoshi Chiba; Tomoki Okazaki; Hiroshi Hara
  Clinica Chimica Acta, 437, 147, 154, Nov. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Two weeks of one-leg immobilization decreases skeletal muscle respiratory capacity equally in young and elderly men
  Martin Gram; Andreas Vigelsø; Takashi Yokota; Christina Neigaard Hansen; Jørn Wulff Helge; Martin Hey-Mogensen; Flemming Dela
  Experimental Gerontology, 58, 269, 278, Oct. 2014, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Intramyocellular lipid is increased in the skeletal muscle of patients with dilated cardiomyopathy with lowered exercise capacity
  Kagami Hirabayashi; Shintaro Kinugawa; Takashi Yokota; Shingo Takada; Arata Fukushima; Tadashi Suga; Masashige Takahashi; Taisuke Ono; Noriteru Morita; Masashi Omokawa; Kuniaki Harada; Noriko Oyama-Manabe; Hiroaki Shirato; Shouji Matsushima; Koichi Okita; Hiroyuki Tsutsui
  International Journal of Cardiology, 176, 3, 1110, 1112, Oct. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice
  Shingo Takada; Kagami Hirabayashi; Shintaro Kinugawa; Takashi Yokota; Shouji Matsushima; Tadashi Suga; Tomoyasu Kadoguchi; Arata Fukushima; Tsuneaki Homma; Wataru Mizushima; Yoshihiro Masaki; Takaaki Furihata; Ryoichi Katsuyama; Koichi Okita; Hiroyuki Tsutsui
  European Journal of Pharmacology, 740, 690, 696, Oct. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• (Pro)renin receptor in skeletal muscle is involved in the development of insulin resistance associated with postinfarct heart failure in mice
  Arata Fukushima; Shintaro Kinugawa; Shingo Takada; Shouji Matsushima; Mochamad Ali Sobirin; Taisuke Ono; Masashige Takahashi; Tadashi Suga; Tsuneaki Homma; Yoshihiro Masaki; Takaaki Furihata; Tomoyasu Kadoguchi; Takashi Yokota; Koichi Okita; Hiroyuki Tsutsui
  American Journal of Physiology-Endocrinology and Metabolism, 307, 6, E503, E514, 15 Sep. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Clinical characteristics and CHADS2 score in patients with heart failure and atrial fibrillation: Insights from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD)
  Sanae Hamaguchi; Shintaro Kinugawa; Shouji Matsushima; Arata Fukushima; Takashi Yokota; Mamoru Sakakibara; Hisashi Yokoshiki; Miyuki Tsuchihashi-Makaya; Hiroyuki Tsutsui
  International Journal of Cardiology, 176, 1, 239, 242, Sep. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Combination of Exercise Training and Diet Restriction Normalizes Limited Exercise Capacity and Impaired Skeletal Muscle Function in Diet-Induced Diabetic Mice
  Tadashi Suga; Shintaro Kinugawa; Shingo Takada; Tomoyasu Kadoguchi; Arata Fukushima; Tsuneaki Homma; Yoshihiro Masaki; Takaaki Furihata; Masashige Takahashi; Mochamad A. Sobirin; Taisuke Ono; Kagami Hirabayashi; Takashi Yokota; Shinya Tanaka; Koichi Okita; Hiroyuki Tsutsui
  Endocrinology, 155, 1, 68, 80, 01 Jan. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Decreased serum brain-derived neurotrophic factor levels are correlated with exercise intolerance in patients with heart failure
  Arata Fukushima; Shintaro Kinugawa; Tsuneaki Homma; Yoshihiro Masaki; Takaaki Furihata; Takashi Yokota; Shouji Matsushima; Takahiro Abe; Tadashi Suga; Shingo Takada; Tomoyasu Kadoguchi; Ryoichi Katsuyama; Koji Oba; Koichi Okita; Hiroyuki Tsutsui
  International Journal of Cardiology, 168, 5, e142, e144, Elsevier BV, Oct. 2013, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Systemic Oxidative Stress Is Associated With Lower Aerobic Capacity and Impaired Skeletal Muscle Energy Metabolism in Patients With Metabolic Syndrome
  Takashi Yokota; Shintaro Kinugawa; Mayumi Yamato; Kagami Hirabayashi; Tadashi Suga; Shingo Takada; Kuniaki Harada; Noriteru Morita; Noriko Oyama-Manabe; Yasuka Kikuchi; Koichi Okita; Hiroyuki Tsutsui
  Diabetes Care, 36, 5, 1341, 1346, 13 Apr. 2013, [Peer-reviewed], [Lead author], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Angiotensin II receptor blocker improves the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice
  Shingo Takada; Shintaro Kinugawa; Kagami Hirabayashi; Tadashi Suga; Takashi Yokota; Masashige Takahashi; Arata Fukushima; Tsuneaki Homma; Taisuke Ono; Mochamad A. Sobirin; Yoshihiro Masaki; Wataru Mizushima; Tomoyasu Kadoguchi; Koichi Okita; Hiroyuki Tsutsui
  Journal of Applied Physiology, 114, 7, 844, 857, 01 Apr. 2013, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Acute Hemodynamic Effects of Adaptive Servo-Ventilation in Patients With Heart Failure
  Shiro Yamada; Mamoru Sakakibara; Takashi Yokota; Kiwamu Kamiya; Naoya Asakawa; Hiroyuki Iwano; Satoshi Yamada; Koji Oba; Hiroyuki Tsutsui
  Circulation Journal, 77, 5, 1214, 1220, Japanese Circulation Society, 2013, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Clinical characteristics and outcomes of dilated phase of hypertrophic cardiomyopathy: Report from the registry data in Japan
  Daisuke Goto; Shintaro Kinugawa; Sanae Hamaguchi; Mamoru Sakakibara; Miyuki Tsuchihashi-Makaya; Takashi Yokota; Satoshi Yamada; Hisashi Yokoshiki; Hiroyuki Tsutsui
  Journal of Cardiology, 61, 1, 65, 70, Jan. 2013, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Low-intensity exercise can increase muscle mass and strength proportionally to enhanced metabolic stress under ischemic conditions
  Shingo Takada; Koichi Okita; Tadashi Suga; Masashi Omokawa; Tomoyasu Kadoguchi; Takashi Sato; Masashige Takahashi; Takashi Yokota; Kagami Hirabayashi; Noriteru Morita; Masahiro Horiuchi; Shintaro Kinugawa; Hiroyuki Tsutsui
  Journal of Applied Physiology, 113, 2, 199, 205, 15 Jul. 2012, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Effect of multiple set on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction
  Tadashi Suga; Koichi Okita; Shingo Takada; Masashi Omokawa; Tomoyasu Kadoguchi; Takashi Yokota; Kagami Hirabayashi; Masashige Takahashi; Noriteru Morita; Masahiro Horiuchi; Shintaro Kinugawa; Hiroyuki Tsutsui
  European Journal of Applied Physiology, 112, 11, 3915, 3920, 14 Mar. 2012, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Blood Flow Restriction Exercise in Sprinters and Endurance Runners
  Shingo Takada; Koichi Okita; Tadashi Suga; Masashi Omokawa; Noriteru Morita; Masahiro Horiuchi; Tomoyasu Kadoguchi; Masashige Takahashi; Kagami Hirabayashi; Takashi Yokota; Shintaro Kinugawa; Hiroyuki Tsutsui
  Medicine & Science in Sports & Exercise, 44, 3, 413, 419, Mar. 2012, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Angiotensin II-induced reduction in exercise capacity is associated with increased oxidative stress in skeletal muscle
  Naoki Inoue; Shintaro Kinugawa; Tadashi Suga; Takashi Yokota; Kagami Hirabayashi; Satoshi Kuroda; Koichi Okita; Hiroyuki Tsutsui
  American Journal of Physiology-Heart and Circulatory Physiology, 302, 5, H1202, H1210, 01 Mar. 2012, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Sleep-Disordered Breathing Is an Independent Risk Factor of Aborted Sudden Cardiac Arrest in Patients With Coronary Artery Spasm
  Mamoru Sakakibara; Shiro Yamada; Kiwamu Kamiya; Takashi Yokota; Koji Oba; Hiroyuki Tsutsui
  Circulation Journal, 76, 9, 2204, 2210, Japanese Circulation Society, 2012, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Hyperuricemia predicts adverse outcomes in patients with heart failure
  Sanae Hamaguchi; Tomoo Furumoto; Miyuki Tsuchihashi-Makaya; Kazutomo Goto; Daisuke Goto; Takashi Yokota; Shintaro Kinugawa; Hisashi Yokoshiki; Akira Takeshita; Hiroyuki Tsutsui
  International Journal of Cardiology, 151, 2, 143, 147, Sep. 2011, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Lower aerobic capacity was associated with abnormal intramuscular energetics in patients with metabolic syndrome
  Takashi Yokota; Shintaro Kinugawa; Koichi Okita; Kagami Hirabayashi; Tadashi Suga; Masaaki Hattori; Yoshinao Nakagawa; Noriko Oyama-Manabe; Hiroki Shirato; Hiroyuki Tsutsui
  Hypertension Research, 34, 9, 1029, 1034, 14 Jul. 2011, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal
• Oxidative stress impairs insulin signal in skeletal muscle and causes insulin resistance in postinfarct heart failure
  Yukihiro Ohta; Shintaro Kinugawa; Shouji Matsushima; Taisuke Ono; Mochamad A. Sobirin; Naoki Inoue; Takashi Yokota; Kagami Hirabayashi; Hiroyuki Tsutsui
  American Journal of Physiology-Heart and Circulatory Physiology, 300, 5, H1637, H1644, May 2011, [International Magazine]
  English, Scientific journal
• Predictors of Long-Term Adverse Outcomes in Elderly Patients Over 80 Years Hospitalized With Heart Failure - A Report From the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) -
  Sanae Hamaguchi; Shintaro Kinugawa; Daisuke Goto; Miyuki Tsuchihashi-Makaya; Takashi Yokota; Satoshi Yamada; Hisashi Yokoshiki; Akira Takeshita; Hiroyuki Tsutsui; JCARE-CARD Investigators
  Circulation Journal, 75, 10, 2403, 2410, 2011, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure
  Sanae Hamaguchi; Shintaro Kinugawa; Miyuki Tsuchihashi-Makaya; Kazutomo Goto; Daisuke Goto; Takashi Yokota; Satoshi Yamada; Hisashi Yokoshiki; Akira Takeshita; Hiroyuki Tsutsui
  American Heart Journal, 160, 6, 1156, 1162, Dec. 2010, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Estimation of skeletal muscle energy metabolism in Machado‐Joseph disease using ³¹P‐MR spectroscopy
  Ichiro Yabe; Khin K. Tha; Takashi Yokota; Kazunori Sato; Hiroyuki Soma; Asako Takei; Satoshi Terae; Koichi Okita; Hidenao Sasaki
  Movement Disorders, 26, 1, 165, 168, Wiley, 03 Sep. 2010, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Abstract
  
  The aim of this study was to determine if muscle energy metabolism, as measured by ³¹P‐magnetic resonance spectroscopy (MRS), is a metabolic marker for the efficacy of treatment of Machado‐Joseph disease (MJD). We obtained ³¹P‐MRS in the calf muscle of 8 male patients with MJD and 11 healthy men before, during, and after a 4 minute plantar flexion exercise in a supine position. The data showed that there was a significant difference between the groups in terms of the PCr/(Pi + PCr) ratio at rest (P = 0.03) and the maximum rate of mitochondrial ATP production (V_max) (P < 0.01). In addition, V_max was inversely correlated with the scale for the assessment and rating of ataxia score (r = −0.34, P = 0.04). The MJD group also showed a reduction in V_max over the course of 2 years (P < 0.05). These data suggest that this noninvasive measurement of muscle energy metabolism may represent a surrogate marker for MJD. © 2010 Movement Disorder Society
• Dose effect on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction
  Tadashi Suga; Koichi Okita; Noriteru Morita; Takashi Yokota; Kagami Hirabayashi; Masahiro Horiuchi; Shingo Takada; Masashi Omokawa; Shintaro Kinugawa; Hiroyuki Tsutsui
  Journal of Applied Physiology, 108, 6, 1563, 1567, American Physiological Society, Jun. 2010, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Our previous study reported that metabolic stress in skeletal muscle achieved by combining moderate blood flow restriction (BFR) with low-intensity resistance exercise at 20% of one repetition maximum (1 RM) could not reach the level achieved by high-intensity resistance exercise. Since the previous protocol is typical of current regimens of this type, we sought in this study to optimize the exercise protocol for low-intensity resistance exercise with BFR by examining the dose effects of exercise intensity and pressure. Twelve healthy subjects participated in this study. They were asked to perform unilateral plantar flexion for 2 min (30 repetitions/min) under six different conditions: two resistance exercises (20% 1 RM and 65% 1 RM) without BFR, and four BFR protocols. The four BFR protocols included three different exercise intensities (20, 30, and 40% 1 RM) with moderate pressure (MP) using 130% of systolic blood pressure (147 ± 17 mmHg, mean ± SD) and 20% 1 RM with high pressure at 200 mmHg. Intramuscular metabolites and pH were obtained by ³¹P-magnetic resonance spectroscopy. Significant dose effects on intramuscular metabolites and pH were observed for exercise intensity ( P < 0.001) but not for BFR pressure. The BFR protocol combining 30% 1 RM with MP had similar results as the high-intensity load at 65% 1 RM. Intramuscular metabolic stress during BFR exercise might be susceptible to increasing exercise intensity. To replace high-intensity resistance exercise, the BFR protocol might require an intensity of ≥30% 1 RM.
• Beta-Blocker Use at Discharge in Patients Hospitalized for Heart Failure Is Associated With Improved Survival
  Miyuki Tsuchihashi-Makaya; Shintaro Kinugawa; Hisashi Yokoshiki; Sanae Hamaguchi; Takashi Yokota; Daisuke Goto; Kazutomo Goto; Akira Takeshita; Hiroyuki Tsutsui; The JCARE-CARD Investigators
  Circulation Journal, 74, 7, 1364, 1371, 2010, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Body Mass Index Is an Independent Predictor of Long-Term Outcomes in Patients Hospitalized With Heart Failure in Japan - A Report From the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) -
  Sanae Hamaguchi; Miyuki Tsuchihashi-Makaya; Shintaro Kinugawa; Daisuke Goto; Takashi Yokota; Kazutomo Goto; Satoshi Yamada; Hisashi Yokoshiki; Akira Takeshita; Hiroyuki Tsutsui; for the JCARE-CARD Investigators
  Circulation Journal, 74, 12, 2605, 2611, 2010, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Oxidative stress in cardiac and skeletal muscle dysfunction associated with diabetes mellitus
  Hiroyuki Tsutsui; Shintaro Kinugawa; Shouji Matsushima; Takashi Yokota
  Journal of Clinical Biochemistry and Nutrition, 48, 1, 68, 71, 2010, [Peer-reviewed], [Invited], [Last author], [International Magazine]
  English, Scientific journal
• Effects of Oral Single-Dose Administration of Sarpogrelate Hydrochloride on Saturation O2 of Calf Muscle During Plantar Flexion Exercise
  Masahiro Horiuchi; Koichi Okita; Shingo Takada; Masashi Omokawa; Tadashi Suga; Noriteru Morita; Kagami Hirabayashi; Takashi Yokota; Shintaro Kinugawa; Hiroyuki Tsutsui
  Advances in Experimental Medicine and Biology, 531, 536, 24 Oct. 2009, [Peer-reviewed], [International Magazine]
  English, In book
• Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice
  Takashi Yokota; Shintaro Kinugawa; Kagami Hirabayashi; Shouji Matsushima; Naoki Inoue; Yukihiro Ohta; Sanae Hamaguchi; Mochamad A. Sobirin; Taisuke Ono; Tadashi Suga; Satoshi Kuroda; Shinya Tanaka; Fumio Terasaki; Koichi Okita; Hiroyuki Tsutsui
  American Journal of Physiology-Heart and Circulatory Physiology, 297, 3, H1069, H1077, Sep. 2009, [Peer-reviewed], [Lead author], [International Magazine]
  English, Scientific journal
• Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes
  Shouji Matsushima; Shintaro Kinugawa; Takashi Yokota; Naoki Inoue; Yukihiro Ohta; Sanae Hamaguchi; Hiroyuki Tsutsui
  American Journal of Physiology-Heart and Circulatory Physiology, 297, 1, H409, H416, Jul. 2009, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Intramuscular metabolism during low-intensity resistance exercise with blood flow restriction
  Tadashi Suga; Koichi Okita; Noriteru Morita; Takashi Yokota; Kagami Hirabayashi; Masahiro Horiuchi; Shingo Takada; Tomohiro Takahashi; Masashi Omokawa; Shintaro Kinugawa; Hiroyuki Tsutsui
  Journal of Applied Physiology, 106, 4, 1119, 1124, Apr. 2009, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Effects of Atrial Fibrillation on Long-Term Outcomes in Patients Hospitalized for Heart Failure in Japan A Report From the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD)
  Sanae Hamaguchi; Hisashi Yokoshiki; Shintaro Kinugawa; Miyuki Tsuchihashi-Makaya; Takashi Yokota; Akira Takeshita; Hiroyuki Tsutsui; The JCARE-CARD Investigators
  Circulation Journal, 73, 11, 2084, 2090, 2009, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Characteristics and Outcomes of Hospitalized Patients With Heart Failure and Reduced vs Preserved Ejection Fraction A Report From the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD)
  Miyuki Tsuchihashi-Makaya; Sanae Hamaguchi; Shintaro Kinugawa; Takashi Yokota; Daisuke Goto; Hisashi Yokoshiki; Norihiro Kato; Akira Takeshita; Hiroyuki Tsutsui; for the JCARE-CARD Investigators
  Circulation Journal, 73, 10, 1893, 1900, 2009, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Anemia is an Independent Predictor of Long-Term Adverse Outcomes in Patients Hospitalized With Heart Failure in Japan A Report From the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD)
  Sanae Hamaguchi; Miyuki Tsuchihashi-Makaya; Shintaro Kinugawa; Takashi Yokota; Akira Takeshita; Hisashi Yokoshiki; Hiroyuki Tsutsui; The JCARE-CARD Investigators
  Circulation Journal, 73, 10, 1901, 1908, 2009, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Chronic Kidney Disease as an Independent Risk for Long-Term Adverse Outcomes in Patients Hospitalized With Heart Failure in Japan Report From the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD)
  Sanae Hamaguchi; Miyuki Tsuchihashi-Makaya; Shintaro Kinugawa; Takashi Yokota; Tomomi Ide; Akira Takeshita; Hiroyuki Tsutsui; The JCARE-CARD Investigators
  Circulation Journal, 73, 8, 1442, 1447, 2009, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Angiotensin II Type 1 Receptor Blocker Attenuates Myocardial Remodeling and Preserves Diastolic Function in Diabatic Heart
  Hiroyuki Tsutsui; Shouji Matsushima; Shintaro Kinugawa; Tomomi Ide; Naoki Inoue; Yukihiro Ohta; Takashi Yokota; Sanae Hamaguchi; Kenji Sunagawa
  Hypertension Research, 30, 5, 439, 449, 2007, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Lower prevalence of circulating natural killer T cells in patients with angina: a potential novel marker for coronary artery disease
  Yasuhiro Andoh; Satoshi Fujii; Kazuya Iwabuchi; Takashi Yokota; Naoki Inoue; Yukihito Nakai; Tetsuya Mishima; Takehiro Yamashita; Toshiaki Nakagawa; Akira Kitabatake; Kazunori Onoe; Hiroyuki Tsutsui
  Coronary Artery Disease, 17, 6, 523, 528, Sep. 2006, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Overexpression of glutathione peroxidase attenuates myocardial remodeling and preserves diastolic function in diabetic heart
  Shouji Matsushima; Shintaro Kinugawa; Tomomi Ide; Hidenori Matsusaka; Naoki Inoue; Yukihiro Ohta; Takashi Yokota; Kenji Sunagawa; Hiroyuki Tsutsui
  American Journal of Physiology - Heart and Circulatory Physiology, 291, 5, H2237, H2245, 2006, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Congenital atrial standstill associated with coinheritance of a novel SCN5A mutation and connexin 40 polymorphisms
  Naomasa Makita; Koji Sasaki; W. Antoinette Groenewegen; Takashi Yokota; Hisashi Yokoshiki; Tomoaki Murakami; Hiroyuki Tsutsui
  Heart Rhythm, 2, 10, 1128, 1134, Oct. 2005, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
  English, Scientific journal
• Mural Thrombus in an Ectatic Right Coronary Artery Caused Acute Myocardial Infarction at Downstream Coronary Artery
  Kazushi Urasawa; Naoki Inoue; Takashi Yokota; Naotsugu Oyama; Hidetsugu Sakai; Satoshi Fujii; Akira Kitabatake
  International Heart Journal, 46, 2, 313, 316, 2005, [Peer-reviewed], [International Magazine]
  English, Scientific journal

• 脂質異常症の基礎知識
  横田 卓, 北海道大学病院のおいしい健康ごはん (増補改訂版), 54, 55, Oct. 2025
  Japanese, Others
• 高血圧の基礎知識
  横田 卓, 北海道大学病院のおいしい健康ごはん (増補改訂版), 18, 19, Oct. 2025
  Japanese, Others
• Becker型筋ジストロフィーの兄弟剖検症例の病理組織学的検討
  宮本裕也; 種井善一; 谷川聖; 小田義崇; 津田真寿美; 加納崇裕; 横田 卓; 矢部一郎; 田中伸哉, 日本病理学会会誌, 112, 1, 378, Mar. 2023
  Japanese
• 肺動脈性肺高血圧症における肺拡散能力低下の機序及び臨床的意義
  杉本絢子; 辻野一三; 辻野一三; 島秀起; 中村順一; 佐藤隆博; 佐藤隆博; 清水薫子; 横田卓; 今野哲; 今野哲, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 8th, 2023
• SGLT2阻害薬はミトコンドリア機能の改善を介し膵β細胞量・機能を保護する
  山内 裕貴; 中村 昭伸; 横田 卓; 高橋 清彦; 川田 晋一朗; 土田 和久; 大森 一乃; 野本 博司; 亀田 啓; 曹 圭龍; 安斉 俊久; 田中 伸哉; 寺内 康夫; 三好 秀明; 渥美 達也, 日本内分泌学会雑誌, 98, 1, 361, 361, Apr. 2022
  (一社)日本内分泌学会, Japanese, Summary national conference
• Suppression of Mitochondrial Oxidative Stress and Atrial Fibrillation Inducibility by SGLT2 Inhibitors in Diabetic Rats
  小泉 拓也; 渡邉 昌也; 横田 卓; 夏井 宏征; 門坂 崇秀; 甲谷 太郎; 中尾 元基; 萩原 光; 鎌田 塁; 天満 太郎; 安斉 俊久, 日本循環器学会学術集会抄録集, 84, Mar. 2022
  English
• 心不全合併腎性貧血患者におけるHIF-PH阻害薬の有効性の検証:多施設・前向き・無作為割付・エンドポイント盲検化研究
  松島将士; 橋本亨; 向井靖; 長友大輔; 桑原志実; 鬼塚健; 横田卓; 齋藤晶理; 絹川真太郎, 日本心臓病学会学術集会(Web), 70th, 2022
• SGLT2阻害薬による膵β細胞保護作用の機序の解明
  山内裕貴; 中村昭伸; 横田卓; 高橋清彦; 川田晋一朗; 土田和久; 大森一乃; 野本博司; 亀田啓; 曹圭龍; 曹圭龍; 安斉俊久; 田中伸哉; 田中伸哉; 寺内康夫; 三好秀明; 三好秀明; 渥美達也, 日本糖尿病・肥満動物学会年次学術集会プログラム・講演抄録集, 35th (CD-ROM), 2022
• Future of Heart Failure Treatment and Cardiac Rehabilitation
  Takashi Yokota, 北海道医報生涯教育シリーズXXIII, 1238, 40, 43, Nov. 2021, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction other
• Improved Mitochondria! Function by Luseogliflozin Prevents Pancreatic Beta-Cell Damage
  Yuki Yamauchi; Akinobu Nakamura; Takashi Yokota; Kiyohiko Takahashi; Shinichiro Kawata; Kazuhisa Tsuchida; Kazuno Omori; Hiroshi Nomoto; Hiraku Kameda; Kyuyong Cho; Toshihisa Anzai; Shinya Tanaka; Yasuo Terauchi; Hideaki Miyoshi; Tatsuya Atsumi, DIABETES, 70, Jun. 2021
  English, Summary international conference
• SGLT2阻害薬はミトコンドリア機能の改善を介し膵β細胞を保護する
  山内 裕貴; 中村 昭伸; 横田 卓; 高橋 清彦; 川田 晋一朗; 土田 和久; 大森 一乃; 野本 博司; 亀田 啓; 曹 圭龍; 安斉 俊久; 田中 伸哉; 寺内 康夫; 三好 秀明; 渥美 達也, 糖尿病, 64, Suppl.1, 6, 6, Apr. 2021
  Japanese, Summary national conference
• Utilization of smartphone app for improving individual lifestyle
  Takashi Yokota, Japanese Journal of Exercise Therapy and Prevention, 22, 2, 15, 18, 2021, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction scientific journal
• Role of intestinal α-defensins in heart failure progression
  Takashi Yokota, The Cell, 52, 7, 42, 43, Jun. 2020, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Report scientific journal
• Empagliflozin Restores Lowered Exercise Endurance Capacity via the Activation of Skeletal Muscle Fatty Acid Oxidation in Murine Heart Failure
  Hideo Nambu; Shingo Takada; Satoshi Maekawa; Naoya Kakutani; Takaaki Furihata; Akimichi Saito; Arata Fukushima; Takashi Yokota; Shintaro Kinugawa, CIRCULATION, 140, Nov. 2019
  English, Summary international conference
• Role of intestinal α-defensins in heart failure progression
  Takashi Yokota, Medical Science Direct, 45, 11, 40, 41, Oct. 2019, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction scientific journal
• 急性・慢性心不全ガイドライン2017年改訂版 後編 ～心不全の治療について～
  横田 卓, すこやかハート (北海道心臓協会), 137, 1, 5, Oct. 2019, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction other
• 心不全管理チェックリストを用いた多職種協働介入は栄養状態やアウトカムを改善させる
  池田 陽子; 熊谷 聡美; 坪田 麻未; 長崎 大亮; 阿部 隆宏; 横田 卓; 福島 新; 武田 宏司, JSPEN, 1, Suppl., 539, 539, Sep. 2019
  Japanese, Summary national conference
• 心不全患者における骨格筋輝度は運動耐容能と関連する
  高田 真吾; 福島 新; 仲野 一平; 角谷 尚哉; 横田 卓; 沖田 孝一; 絹川 真太郎, 日本臨床運動療法学会学術集会プログラム・抄録集, 38, 58, 58, Aug. 2019
  Japanese, Summary national conference
• 急性・慢性心不全ガイドライン2017年改訂版 前編 ～心不全の診断について～
  横田 卓, すこやかハート (北海道心臓協会), 136, 1, 3, Jun. 2019, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction other
• Heart failure management using ICT
  Takashi Yokota, Heart Failure (2nd edition), 77, 556, 560, May 2019, [Invited], [Corresponding author]
  Japanese, Introduction scientific journal
• 動物実験従事者におけるアレルギー健診5年分の経年的解析
  吉村 彩; 武藏 学; 折戸 智恵子; 川原 由佳子; 横田 卓; 大西 俊介; 橋野 聡, CAMPUS HEALTH, 56, 1, 239, 241, Mar. 2019, [Invited]
  Japanese, Introduction scientific journal
• Mechanisms of Ventilatory Efficiency during Exercise in Heart Failure: Comparison between Heart Failure with Preserved Ejection Fraction and Reduced Ejection Fraction(和訳中)
  辻永 真吾; 岩野 弘幸; 更科 美羽; 村山 迪史; 中鉢 雅大; 横山 しのぶ; 西野 久雄; 岡田 一範; 加賀 早苗; 福島 新; 横田 卓; 安斉 俊久, 日本循環器学会学術集会抄録集, 83回, OJ08, 2, Mar. 2019
  (一社)日本循環器学会, English
• 在宅でのICTを活用した心不全患者向けセルフケア強化システムの開発・検証
  髙田 真吾; 絹川 真太郎; 横田 卓, 福田記念医療技術振興財団情報, 31, 99, 103, Dec. 2018
  福田記念医療技術振興財団, Japanese
• The Outer Mitochondrial Membrane Protein, mitoNEET, Sustains Structure of Mitochondrial Cristae
  Takaaki Furihata; Shintaro Kinugawa; Shingo Takada; Satoshi Maekawa; Takashi Katayama; Ryosuke Shirakawa; Hideo Nambu; Yoshikuni Obata; Katsuma Yamanashi; Naoya Kakutani; Akimichi Saito; Arata Fukushima; Takashi Yokota; Toshihisa Anzai, CIRCULATION, 138, Nov. 2018
  English, Summary international conference
• Inhibition of Xanthine Oxidase in the Acute Phase Preserves Mitochondrial Function in Skeletal Muscle and Exercise Capacity in Heart Failure After Myocardial Infarction
  Hideo Nambu; Shingo Takada; Satoshi Maekawa; Junichi Matsumoto; Naoya Kakutani; Ryosuke Shirakawa; Takashi Katayama; Katsuma Yamanashi; Yoshikuni Obata; Takaaki Furihata; Akimichi Saito; Takashi Yokota; Shintaro Kinugawa; Toshihisa Anzai, CIRCULATION, 138, Nov. 2018
  English, Summary international conference
• Excessive Mitochondrial Reactive Oxygen Species Emission From Circulating Blood Cells is Associated With Systemic Oxidative Stress, Severity of Heart Failure, and Exercise Intolerance
  Ryosuke Shirakawa; Takashi Yokota; Takayuki Nakajima; Shingo Takada; Miwako Yamane; Akimichi Saito; Satoshi Maekawa; Naoya Kakutani; Takaaki Furihata; Junichi Matsumoto; Masaya Tsuda; Takashi Katayama; Hideo Nambu; Katsuma Yamanashi; Yoshikuni Obata; Ippei Nakano; Arata Fukushima; Shintaro Kinugawa; Toshihisa Anzai, CIRCULATION, 138, Nov. 2018
  English, Summary international conference
• Determinants of Ventilatory Efficiency in Patients With Heart Failure: Incites From Left Ventricular Suction During Exercise
  Shingo Tsujinaga; Hiroyuki Iwano; Miwa Sarashina; Michito Murayama; Masahiro Nakabachi; Shinobu Yokoyama; Hisao Nishino; Arata Fukushima; Takashi Yokota; Pavlos P. Vlachos; Toshihisa Anzai, CIRCULATION, 138, Nov. 2018
  English, Summary international conference
• 動物実験従事者におけるアレルギー健診5年分の経年的解析
  吉村 彩; 武藏 学; 折戸 智恵子; 川原 由佳子; 横田 卓; 大西 俊介; 橋野 聡, 全国大学保健管理研究集会プログラム・抄録集, 56, 70, 70, Sep. 2018
  Japanese, Summary national conference
• 心疾患に対する運動療法・リハビリテーションの実際
  角谷 尚哉; 阿部 隆宏; 横田 卓, 心不全と骨格筋機能障害 (文光堂) 沖田 孝一 著, 100, 139, Jul. 2018, [Invited]
  Japanese, Introduction other
• Clinical and Basic Investigations on the Serum Adropin as a Surrogate Marker for Age-Related Exercise Intolerance and Sarcopenia
  福島新; 絹川真太郎; 横田卓; 高田真吾; 沖田孝一, デサントスポーツ科学, 39, 76, 83, May 2018
  石本記念デサントスポーツ科学振興財団事務局, Japanese
• ICTによる心不全の次世代型疾病管理
  横田 卓, 月刊「循環器内科」 (科学評論社), 83, 2, 133, 137, Feb. 2018, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction scientific journal
• Mitochondrial Dysfunction in Epicardial Adipose Tissue is Associated with Coronary Artery Stenosis
  NAKAJIMA Takayuki; YOKOTA Takashi; SHINGU Yasushige; YAMADA Akira; IBA Yutaka; UJIHIRA Kosuke; WAKASA Satoru; OOKA Tomonori; TAKADA Shingo; SHIRAKAWA Ryosuke; FURIHATA Takaaki; TSUDA Masaya; MATSUMOTO Junichi; KATAYAMA Takashi; FUKUSHIMA Arata; SAITO Akimichi; MATSUOKA Ryosuke; NISHIHARA Hiroshi; MATSUI Yoshiro; KINUGAWA Shintaro, 日本循環器学会学術集会(Web), 82nd, 2018
• ICTによる心不全の疾病管理
  横田 卓, 月刊「Heart View」(メジカルビュー社), 12, 55, 59, 2018, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction scientific journal
• 心不全の原因特定にはどのようなタイミングでどのようなアプローチが理想的ですか？
  横田 卓, 羊土社レジデントノート増刊「循環器疾患のギモン、百戦錬磨のエキスパートが答えます！」, 20, 5, 694, 700, 2018, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction other
• 多職種カンファレンスで明らかとなった緩和ケアあるいは植込み型補助人工心臓を要する重症心不全の患者像
  阿部隆宏; 福島新; 横田卓; 古山勇気; 長崎大亮; 池田陽子; 大塚広貴; 絹川真太郎; 安斉俊久, 日本心不全学会学術集会プログラム・抄録集, 22nd, 379, 2018
  Japanese
• mitoNEET Regulates Mitochondrial Iron Homeostasis Interacting With Transferrin Receptor
  Takaaki Furihata; Shingo Takada; Wataru Mizushima; Satoshi Maekawa; Arata Fukushima; Masaya Tsuda; Junichi Matsumoto; Naoya Kakutani; Takashi Yokota; Shintaro Kinugawa, CIRCULATION, 136, Nov. 2017
  English, Summary international conference
• Acetylation of Mitochondrial Proteins Alters Fatty Acid beta-Oxidation in Skeletal Muscle and Limits Exercise Capacity in Post-Infarct Heart Failure in Mice
  Masaya Tsuda; Arata Fukushima; Junichi Matsumoto; Shingo Takada; Takashi Yokota; Takaaki Furihata; Takashi Katayama; Takayuki Nakajima; Hideo Nambu; Satoshi Maekawa; Ryosuke Shirakawa; Naoya Kakutani; Yoshikuni Obata; Katsuma Yamanashi; Koichi Okita; Shintaro Kinugawa, CIRCULATION, 136, Nov. 2017
  English, Summary international conference
• High Respiratory Exchange Ratio at Submaximal Exercise Level Predicts Adverse Clinical Outcomes in Patients With Heart Failure
  Naoya Kakutani; Arata Fukushima; Takashi Yokota; Takashi Katayama; Ryosuke Shirakawa; Satoshi Maekawa; Hideo Nambu; Takahiro Abe; Takaaki Furihata; Junichi Matsumoto; Masaya Tsuda; Takayuki Nakajima; Katsuma Yamanashi; Yoshikuni Obata; Shingo Takada; Akimichi Saito; Koichi Okita; Shintaro Kinugawa, CIRCULATION, 136, Nov. 2017
  English, Summary international conference
• Coronary Artery Stenosis is Associated With Mitochondrial Dysfunction in Epicardial Adipose Tissue
  Takayuki Nakajima; Takashi Yokota; Yasushige Shingu; Akira Yamada; Yutaka Iba; Kosuke Ujihara; Shuhei Miura; Shingo Takada; Ryosuke Shirakawa; Takaaki Furihata; Masaya Tsuda; Junichi Matsumoto; Takashi Katayama; Arata Fukushima; Akimichi Saito; Yoshiro Matsui; Shintaro Kinugawa, CIRCULATION, 136, Nov. 2017
  English, Summary international conference
• Skeletal Muscle Mitochondrial Protein Hyperacetylation Contributes to Exercise Intolerance in a Murine Model of Heart Failure After Myocardial Infarction(和訳中)
  津田 正哉; 高田 真吾; 福島 新; 水島 航; 降旗 高明; 松本 純一; 片山 貴史; 中島 孝之; 白川 亮介; 前川 聡; 南部 秀雄; 角谷 尚哉; 横田 卓; 絹川 真太郎, 日本循環器学会学術集会抄録集, 81回, PJ, 044, Mar. 2017
  (一社)日本循環器学会, English
• The Novel Heart-specific RING-finger Protein 207 Modulates Energy Metabolism in Cardiomyocytes(和訳中)
  高田 真吾; 水島 航; 降旗 高明; 松本 純一; 津田 正哉; 片山 貴史; 中島 孝之; 福島 新; 横田 卓; 絹川 真太郎, 日本循環器学会学術集会抄録集, 81回, PJ, 066, Mar. 2017
  (一社)日本循環器学会, English
• Mitochondrial Dysfunction in Epicardial Adipose Tissue is Associated with Coronary Artery Stenosis(和訳中)
  中島 孝之; 横田 卓; 新宮 康栄; 山田 陽; 伊庭 裕; 若狭 哲; 大岡 智学; 高田 真吾; 白川 亮介; 降旗 高明; 津田 正哉; 松本 純一; 片山 貴史; 福島 新; 松居 喜郎; 絹川 真太郎, 日本循環器学会学術集会抄録集, 81回, PJ, 075, Mar. 2017
  (一社)日本循環器学会, English
• Cardiac Hypertrophy in Congenital Heart Disease Delays the Maturation of Cardiac Fatty Acid B-Oxidation by Modifying Myocardial Acetylation Control(和訳中)
  福島 新; 絹川 真太郎; 横田 卓; 齋藤 晶理; 高田 真吾; 降旗 高明; 松本 純一; 津田 正哉; 中島 孝之; 片山 貴史; 前川 聡; 南部 秀雄; 角谷 尚哉; 白川 亮介; 沖田 孝一; ポール・カンター; アイバン・レベッカ; ギャリー・ロパスチュック, 日本循環器学会学術集会抄録集, 81回, PJ, 400, Mar. 2017
  (一社)日本循環器学会, English
• Protein Acetylation in Skeletal Muscle Impairs Mitochondrial Fatty Acid Oxidation and Limits Exercise Capacity in Post-Infarct Heart Failure in Mice
  YAMANASHI Katsuma; TSUDA Masaya; FUKUSHIMA Arata; TAKADA Shingo; FURIHATA Takaaki; MATSUMOTO Junichi; MAEKAWA Satoshi; KATAYAMA Takashi; YOKOTA Takashi; KINUGAWA Shintaro, 日本心不全学会学術集会プログラム・抄録集, 21st, 2017
• Mitochondrial dysfunction in epicardial adipose tissue from patients with coronary artery disease
  NAKAJIMA Takayuki; YOKOTA Takashi; SINGU Yasushige; YAMADA Akira; IBA Yutaka; UJIHIRA Kosuke; TAKADA Shingo; SIRAKAWA Ryosuke; FURIHATA Takaaki; TSUDA Masaya; MATSUMOTO Junichi; KATAYAMA Takashi; FUKUSHIMA Arata; MATSUI Yoshiro; KINUGAWA Shintaro, 日本心血管内分泌代謝学会学術総会プログラム及び抄録集, 21st, 2017
• Underweight is an Independent Predictor of Outcomes in Heart Failure with Preserved Ejection Fraction: A Report from JASPER Study
  MATSUMOTO Junichi; KINUGAWA Shintaro; FUKUSHIMA Arata; YOKOTA Takashi; YOSHIKAWA Tsutomu; SAITO Yoshihiko; NAGAI Toshiyuki; ANZAI Toshihisa, 日本循環器学会学術集会(Web), 81st, 2017
• Brain-Derived Neurotrophic Factor Improves Mitochondrial Function via Upregulation of Fatty-Acid Oxidation in the Skeletal Muscle of Mice with Heart Failure
  MATSUMOTO Junichi; TAKADA Shingo; FURIHATA Takaaki; TSUDA Masaya; NAKAJIMA Takayuki; KATAYAMA Takashi; NAMBU Hideo; SHIRAKAWA Ryosuke; MAEKAWA Satoshi; KAKUTANI Naoya; MIZUSHIMA Wataru; FUKUSHIMA Arata; YOKOTA Takashi; KINUGAWA Shintaro, 日本循環器学会学術集会(Web), 81st, 2017
• 心不全を合併したLoeys-Diez症候群の一例
  横田卓; 津田正哉; 松島将士, 日本循環器学会北海道地方会(Web), 118th, 2017
• 心血管病を予防するための運動療法～運動療法の効果について～ (後編)
  横田 卓, すこやかハート (北海道心臓協会), 131, 2017, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction other
• 心血管病を予防するための運動療法～運動療法の効果について～ (前編)
  横田 卓, すこやかハート (北海道心臓協会), 130, 2017, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction other
• 心不全診療におけるICTの活用
  横田 卓, 適応医学, 21, 2, 8, 13, 2017, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction scientific journal
• 【基礎研究を予防心臓病学の未来に活かす】 心不全における骨格筋萎縮予防
  沖田 孝一; 高田 真吾; 横田 卓; 絹川 真太郎, 心臓リハビリテーション, 22, 2-3, 132, 135, Jan. 2017
  (NPO)日本心臓リハビリテーション学会, Japanese
• Brain-derived Neurotrophic Factor Plays an Important Role of Exercise Capacity and Mitochondrial Function in the Skeletal Muscle in Mice With Post-infarct Heart Failure
  Takayuki Nakajima; Shintaro Kinugawa; Junichi Matsumoto; Shingo Takada; Takaaki Furihata; Masaya Tsuda; Takashi Katayama; Hideo Nanbu; Ryosuke Shirakawa; Satoshi Maekawa; Naoya Kakutani; Wataru Mizushima; Takashi Yokota; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 134, Nov. 2016
  English, Summary international conference
• Mitochondrial Protein Acetylation in Skeletal Muscle Was Associated With Exercise Intolerance in Heart Failure After Myocardial Infarction in Mice
  Masaya Tsuda; Shintaro Kinugawa; Shingo Takada; Arata Fukushima; Takashi Yokota; Wataru Mizushima; Takaaki Furihata; Junichi Matsumoto; Takashi Katayama; Takayuki Nakajima; Satoshi Maekawa; Hideo Nambu; Ryosuke Shirakawa; Naoya Kakutani; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 134, Nov. 2016
  English, Summary international conference
• The Activation of Glucagon-Like Peptide-1 Improves the Mitochondrial Abnormalities in Skeletal Muscle and Exercise Intolerance in Heart Failure Mice
  Takashi Katayama; Shingo Takada; Yoshihiro Masaki; Shintaro Kinugawa; Junichi Matsumoto; Takayuki Nakajima; Masaya Tsuda; Takaaki Furihata; Wataru Mizushima; Arata Fukushima; Takashi Yokota; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 134, Nov. 2016
  English, Summary international conference
• Plasma Acetyl-lysine is a Novel Marker for Exercise Capacity in Patients With Heart Failure
  Masaya Tsuda; Shintaro Kinugawa; Arata Fukushima; Shingo Takada; Takashi Yokota; Takaald Furihata; Junichi Matsumoto; Takashi Katayama; Takayuki Nakajima; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 22, 9, S191, S191, Sep. 2016
  English, Summary international conference
• Pioglitazone Improves Aerobic Capacity and Skeletal Muscle Energy Metabolism in Patients with Metabolic Syndrome
  Takashi Yokota; Shintaro Kinugawa; Kagami Hirabayashi; Tadashi Suga; Shingo Takada; Koichi Okita; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 22, 9, S205, S205, Sep. 2016
  English, Summary international conference
• Brain-Derived Neurotrophic Factor Regulates Exercise Capacity and Mitochondria' Function in the Skeletal Muscle in Mice with Post-Infarct Heart Failure
  Junichi Matsumoto; Shingo Takada; Shintaro Kinugawa; Takaaki Furihata; Masaya Tsuda; Takayuki Nakajima; Takashi Katayama; Wataru Mizushima; Takashi Yokota; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 22, 9, S213, S213, Sep. 2016
  English, Summary international conference
• The Activation of Glucagon-Like Peptide-1 Improves the Mitochondrial Abnormalities in Skeletal Muscle and Exercise Intolerance in Heart Failure Mice
  Takashi Katayama; Shingo Takada; Yoshihiro Masaki; Shintaro Kinugawa; Junichi Matsumoto; Takaaki Furihata; Arata Fukushima; Takashi Yokota; Koichi Okita; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 22, 9, S162, S162, Sep. 2016
  English, Summary international conference
• 高度肥満男子学生における末梢血リンパ球サブセット解析
  吉村 彩; 大西 俊介; 川原 由佳子; 折戸 智恵子; 柏崎 晴彦; 本間 理央; 加納 崇裕; 横田 卓; 橋野 聡, 肥満研究, 22, Suppl., 229, 229, Sep. 2016
  (一社)日本肥満学会, Japanese
• Brain-derived neurotrophic factor improves exercise capacity and mitochondrial function in the skeletal muscle in mice with post-infarct heart failure
  J. Matsumoto; S. Takada; S. Kinugawa; W. Mizushima; T. Furihata; M. Tsuda; T. Nakajima; T. Katayama; T. Yokota; K. Okita; H. Tsutsui, EUROPEAN HEART JOURNAL, 37, 708, 708, Aug. 2016
  English, Summary international conference
• 肥満学生における簡易型自記式食事調査票(BDHQ)の意義について
  折戸 智恵子; 大西 俊介; 川原 由佳子; 吉村 彩; 柏崎 晴彦; 本間 理央; 川久保 和道; 加納 崇裕; 横田 卓; 橋野 聡, CAMPUS HEALTH, 53, 1, 201, 203, Mar. 2016
  本学の2014年定期健診で肥満と判定された学生22名にBDHQ調査を行い、コントロール群11名と比較した。結果、「摂取エネルギー」「炭水化物」「脂質」などの栄養素に有意な群間差はなかったが、食品では「緑黄色野菜」「漬物」「アイスクリーム」「果物」「洋菓子」の摂取量が肥満群で有意に少なかった。BDHQの結果報告には、おおよその信頼度を示す数値として摂取エネルギーの推定申告誤差が表示されており、±30%の範囲であれば、ある程度信頼度が高いとされる。今回の調査では、両群ともに過少申告者が存在したが、肥満群は-30%以上の割合がコントロール群より多く、信頼度が低かった(過少申告率が高かった)。肥満群には栄養・保健指導を行い、4ヵ月後に再度BDHQ調査を行ったところ、過少申告率は更に高くなっていた。, (公社)全国大学保健管理協会, Japanese
• 高度肥満学生における高感度CRPの測定意義について
  吉村 彩; 大西 俊介; 川原 由佳子; 折戸 智恵子; 柏崎 晴彦; 本間 理央; 川久保 和道; 加納 崇裕; 横田 卓; 橋野 聡, CAMPUS HEALTH, 53, 1, 106, 108, Mar. 2016
  (公社)全国大学保健管理協会, Japanese
• mitoNEET Regulates Mitochondrial Iron Homeostasis in the Hearts
  FURIHATA Takaaki; KINUGAWA Shintaro; TAKADA Shingo; MATSUSHIMA Shouji; MIZUSHIMA Wataru; TSUDA Masaya; MATSUMOTO Junichi; YOKOTA Takashi; TSUTSUI Hiroyuki, Circulation Journal, 80, Supplement 1(CD-ROM), 2016
• Recombinant Human BDNF Increases Exercise Capacity and Mitochondrial Function in the Skeletal Muscle
  TAKADA Shingo; KINUGAWA Shintaro; MATSUSHIMA Shouji; YOKOTA Takashi; MIZUSHIMA Wataru; FURIHATA Takaaki; MATSUMOTO Junichi; TSUDA Masaya; NAKAJIMA Takayuki; KATAYAMA Takashi; FUKUSHIMA Arata; OKITA Koichi; TSUTSUI Hiroyuki, Circulation Journal, 80, Supplement 1(CD-ROM), 2016
• Brain-Derived Neurotrophic Factor Regulates Mitochondrial Function through Ampk-Pgc1Α Signaling in the Skeletal Muscle from Mice with Post-infarct Heart Failure
  MATSUMOTO Junichi; KINUGAWA Shintaro; TAKADA Shingo; FURIHATA Takaaki; MIZUSHIMA Wataru; TSUDA Masaya; NAKAJIMA Takayuki; KATAYAMA Takashi; YOKOTA Takashi; MATSUSHIMA Shouji; OKITA Koichi, Circulation Journal, 80, Supplement 1(CD-ROM), 2016
• Increased Plasma Protein Acetylation was Associated with Exercise Intolerance in Patients with Heart Failure Assessed by Global Metabolomic Analysis
  TSUDA Masaya; KINUGAWA Shintaro; FUKUSHIMA Arata; YOKOTA Takashi; MATSUSHIMA Shoji; FURIHATA Takaaki; TAKADA Shingo; MATSUMOTO Junichi; KATAYAMA Takashi; NAKAJIMA Takayuki; OKITA Koichi; TSUTSUI Hiroyuki, Circulation Journal, 80, Supplement 1(CD-ROM), 2016
• mitoNEET Regulates Mitochondrial Iron Contents in the Hearts
  MAEKAWA Satoshi; FURIHATA Takaaki; TAKADA Shingo; FUKUSHIMA Arata; TSUDA Masaya; MATSUMOTO Junichi; YOKOTA Takashi; KINUGAWA Shintaro, 日本心血管内分泌代謝学会学術総会プログラム及び抄録集, 20th, 2016
• 急性期における心不全患者の離床遅延に関連する因子の検討
  石川幸司; 絹川真太郎; 福島新; 横田卓; 松島将士; 筒井裕之, 日本心不全学会学術集会プログラム・抄録集, 20th, 2016
• 急性期における心不全患者の離床遅延と心血管イベントの関連性
  石川幸司; 絹川真太郎; 福島新; 横田卓; 松島将士; 筒井裕之, 日本心不全学会学術集会プログラム・抄録集, 20th, 2016
• CPXを用いた労作時息切れの鑑別
  横田 卓, 包括的心臓リハビリテーションを極める（文光堂; 絹川真太郎編）, 77, 78, 2016, [Invited], [Lead author, Last author, Corresponding author]
  Japanese, Introduction other
• Skeletal Muscle Dysfunction in Diabetes
  Okita Koichi; Takada Shingo; Yokota Takashi; Kinugawa Shintaro, Congress of the Japanese Physical Therapy Association, 43, 0, 95, 95, 2016
  JAPANESE PHYSICAL THERAPY ASSOCIATION, Japanese
• 糖代謝異常にみられる運動耐容能低下と骨格筋障害について
  沖田孝一; 高田真吾; 高橋将成; 平林鑑; 横田卓; 絹川真太郎, 日本臨床運動療法学会雑誌, 18, 1, 45, 2016
  Japanese
• 心不全モデルマウスにおける骨格筋ミトコンドリア機能低下に対する脳由来神経栄養因子の役割解明
  高田 真吾; 絹川 真太郎; 横田 卓; 松島 将士; 沖田 孝一; 筒井 裕之, 体力科学, 64, 6, 599, 599, Dec. 2015
  (一社)日本体力医学会, Japanese
• Brain-Derived Neurotrophic Factor Could Regulate Mitochondrial Function in the Skeletal Muscle Through Ampk-Pgc1 alpha Signaling in Heart Failure Mice
  Takayuki Nakajima; Shintaro Kinugawa; Shingo Takada; Junichi Matsumoto; Wataru Misushima; Takaaki Furihata; Masaya Tsuda; Takashi Yokota; Shouji Matsushima; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 21, 10, S197, S197, Oct. 2015
  English, Summary international conference
• Metabolomic Analysis Reveals New Insights Towards Understanding Skeletal Muscle Mass and Exercise Capacity in Patients with Heart Failure
  Masaya Tsuda; Shintaro Kinugawa; Arata Fukushima; Shingo Takada; Takashi Yokota; Shoji Matsushima; Takaaki Furihata; Junichi Matsumoto; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 21, 10, S195, S195, Oct. 2015
  English, Summary international conference
• 高度肥満学生に対する保健指導前後の血液学的変化および体組成変化の検討
  吉村 彩; 大西 俊介; 川原 由佳子; 折戸 智恵子; 柏崎 晴彦; 本間 理央; 川久保 和道; 加納 崇裕; 横田 卓; 橋野 聡, 肥満研究, 21, Suppl., 154, 154, Sep. 2015
  (一社)日本肥満学会, Japanese
• 特異な左室壁形態を呈した肥大型心筋症の一例
  相川忠夫; 納谷昌直; 神谷究; 横田卓; 松島将士; 筒井裕之, 日本心臓病学会学術集会(Web), 63回, 851, 851, Sep. 2015
  (一社)日本心臓病学会, Japanese
• 高度肥満学生における簡易式自記式食事歴調査票の意義について
  折戸 智恵子; 大西 俊介; 川原 由佳子; 吉村 彩; 本間 理央; 川久保 和道; 加納 崇裕; 横田 卓; 橋野 聡, 全国大学保健管理研究集会プログラム・抄録集, 53回, 58, 58, Aug. 2015
  (公社)全国大学保健管理協会, Japanese
• 高度肥満学生における高感度CRPの測定意義について
  吉村 彩; 大西 俊介; 川原 由佳子; 折戸 智恵子; 本間 理央; 川久保 和道; 加納 崇裕; 横田 卓; 橋野 聡, 全国大学保健管理研究集会プログラム・抄録集, 53回, 36, 36, Aug. 2015
  (公社)全国大学保健管理協会, Japanese
• Resistance Training with Blood Flow Restriction : Optimization in Women
  沖田孝一; 高田真吾; 吉田真; 森田憲輝; 横田卓, デサントスポーツ科学, 36, 99, 105, Jun. 2015
  石本記念デサントスポーツ科学振興財団事務局, Japanese
• 本学での子宮頸がんワクチン接種実施報告 不安と疼痛の影響から考えられたこと
  川原 由佳子; 折戸 智恵子; 吉村 彩; 石原 可愛; 大西 俊介; 横田 卓; 橋野 聡, CAMPUS HEALTH, 52, 1, 231, 233, Mar. 2015
  本学保健センターでは、子宮頸がんワクチン接種を希望する新入生女子24名に対して平成25年6月上旬に1回目の接種をしていたが、同年6月14日に厚労省が積極的勧奨を差し控えたため、7名が途中キャンセルした。今回、キャンセルした学生を含む24名の接種に対する不安について、接種前後の収縮期血圧を指標に調査するとともに、接種時の疼痛についてVAS(0〜10)で調査した。結果、収縮期血圧の平均値は、1回目の接種前が114.3、接種後107、2回目の接種前103.5、接種後99、3回目の接種前105.1、接種後105.6であり、1回目の接種前が最も高く、1回目と2回目は接種前が接種後より高値であったが、3回目は接種前後で差異を認めなかった。VASは、1回目が「0」7名、「1」1名、「2」1名、「3」2名、「5」12名、「6」1名、2回目(19名)が「2」1名、「3」3名、「4」1名、「5」9名、「6」5名、3回目(18名)が「1」4名、「2」2名、「4」2名、「5」7名、「6」2名、「7」1名であった。, (公社)全国大学保健管理協会, Japanese
• 動物実験従事者におけるアレルギー健診3年分の経年的解析
  吉村 彩; 武藏 学; 折戸 智恵子; 川原 由佳子; 横田 卓; 大西 俊介; 橋野 聡, CAMPUS HEALTH, 52, 1, 443, 445, Mar. 2015
  本学では平成22年度に、実験中マウスに噛まれてアナフィラキシーショックを起こした事例があったため、平成23年度から予防対策の一環として、動物実験従事者のうち希望者に対し、取扱動物の特異的IgE抗体検査を含む健診を毎年実施している。昨年度に3回目が終了したので、3年間継続受診した者に着目して経年的な解析を行った。対象者は86名で、3年間継続して同種の抗体検査を実施したものは、マウスIgE抗体65名、ラットIgE抗体44名、ハムスターIgE抗体6名、モルモット2名、ウサギ14名であった。動物別にみた特異的IgE抗体陽性率の経年的変化は、マウスが平成23年度18.5%、24年度23.1%、25年度27.7%、ラットがそれぞれ15.9%、20.5%、22.7%であり、両者とも増加傾向にあるものの有意差はなかった。対象者に対して問診票による調査を行い、抗体陽性率との関連について検討した結果、「眼の症状」「蕁麻疹」がマウスIgE抗体陽性率と有意な関連を示したが、「ペット飼育」「親族のアレルギー歴」「喫煙」「気管支炎」「花粉症」「アトピー性皮膚炎」などはマウス・ラットとも有意な関連は示さなかった。, (公社)全国大学保健管理協会, Japanese
• A Metabolomics Approach Provides New Insights into Exercise Intolerance in Patients with Heart Failure
  TSUDA Masaya; KINUGAWA Shintaro; FUKUSHIMA Arata; MATSUSHIMA Shoji; FURIHATA Takaaki; TAKADA Shingo; KADOGUCHI Tomoyasu; KUDO Masato; MATSUMOTO Junichi; YOKOTA Takashi; OKITA Koichi; TSUTSUI Hiroyuki, Circulation Journal, 79, Supplement 1(CD-ROM), 2015
• Angiotensin II Administration Can Directly Induce Skeletal Muscle Abnormalities and Reduce Exercise Capacity in Mice
  KADOGUCHI Tomoyasu; KINUGAWA Shintaro; FUKUSHIMA Arata; FURIHATA Takaaki; TAKADA Shingo; KUDO Masato; TSUDA Masaya; MATSUMOTO Junichi; YOKOTA Takashi; MATSUSHIMA Shoji; OKITA Koichi; TSUTSUI Hiroyuki, Circulation Journal, 79, Supplement 1(CD-ROM), 2015
• Decreased Brain-Derived Neurotrophic Factor Impairs Mitochondrial Function via Ampk-Pgc1α Signaling in the Skeletal Muscle from Post-infarct Heart Failure Mice.
  MATSUMOTO Junichi; KINUGAWA Shintaro; TAKADA Shingo; FURIHATA Takaaki; MIZUSHIMA Wataru; MATSUSHIMA Shouji; YOKOTA Takashi; TSUTSUI Hiroyuki, 日本血管生物医学会学術集会プログラム・抄録集, 23rd, 2015
• Ring Finger Protein 207 Regulates Cell Death in Cardiomyocytes through Direct Interaction with Voltage-Dependent Anion Channel
  MIZUSHIMA Wataru; KINUGAWA Shintaro; MATSUSHIMA Shoji; TAKADA Shingo; FUKUSHIMA Arata; FURIHATA Takaaki; KUDOU Masato; MATSUMOTO Junichi; TSUDA Masaya; KADOGUCHI Tomoyasu; YOKOTA Takashi; TSUTSUI Hiroyuki, Circulation Journal, 79, Supplement 1(CD-ROM), 2015
• The 6th Asian Congress of Dietetics, August 21-25, 2014, Taipei Taiwan : EFFECTS OF LOW-CARBOHYDRATE DIET ON PHYSICAL STRENGTH
  Okita Koichi; Takada Shingo; Taniura Tomofumi; Morita Noriteru; Kadoguchi Tomoyasu; Sasaki Hiroko; Yokota Takashi; Kinugawa Shintaro; Tsutsui Hiroyuki, Bulletin of the Northern Regions Academic Information Center, Hokusho University, 7, 103, 108, 2015
  近年,肥満症,メタボリック症候群,糖尿病患者の予防・改善を目的とした低糖質食療法が,米国糖尿病学会で推奨され,我が国では,民間を中心に普及してきている。しかしながら,一方で低糖質食が体力面などに与える悪影響が懸念されている。本研究では,低糖質食および総カロリーが体力指標に与える影響を検討した。12人(男性5人,女性7人,平均年齢20才)の被験者を低糖質食と総カロリー制限群に無作為に割り付け,1ヶ月間の介入を施行し,前後において,身体計測,筋力,持久力および血液生化学的検査を行なった。介入後,糖質制限群のみにおいて,体重,体格指数,腹囲およびHbA1c が有意に減少した(p<0.05)。一方,血中ケトン体は,糖質制限群で極めて顕著に増加していた(p<0.05)。膝伸展筋力,最大酸素摂取量および大腿四頭筋厚は,両群で有意な変化および差異を認めなかった。低糖質食では,比較的短期間に有効な減量が得られ,体力面への悪影響は明らかではないことが示された。, Hokusho University, English
• 右室にのみ収縮障害を呈する心サルコイドーシスに持続性心室頻拍が生じた1例
  南部秀雄; 岩野弘幸; 前川聡; 木村銀河; 水上和也; 横田卓; 畑中佳奈子; 納谷昌直; 筒井裕之, 日本循環器学会北海道地方会, 114th, 2015
  Japanese
• 心臓原発undifferentiated/unclassified sarcomaの1例
  前川聡; 岩野弘幸; 南部秀雄; 木村銀河; 水上和也; 横田卓; 菅野宏美; 納谷昌直; 筒井裕之, 日本循環器学会北海道地方会, 113th, 2015
  Japanese
• 心臓原発Undifferentiated/unclassified sarcomaの1例
  前川聡; 岩野弘幸; 南部秀雄; 木村銀河; 水上和也; 横田卓; 岡田宏美; 納谷昌直; 筒井裕之, 日本血管生物医学会学術集会プログラム・抄録集, 23rd, 193, 2015
  Japanese
• 石灰化部位に感染性心内膜炎を生じた心内膜心筋線維症の一例
  相川忠夫; 松島将士; 中島孝之; 笹井春江; 松谷健一; 神谷究; 横田卓; 真鍋治; 納谷昌直; 三橋智子; 松居喜郎; 筒井裕之, 日本血管生物医学会学術集会プログラム・抄録集, 23rd, 184, 2015
  Japanese
• Disruption of Outer Mitochondrial Membrane Protein, MitoNEET, Increases Mitochondrial Iron Content in the Heart
  Takaaki Furihata; Shintaro Kinugawa; Shouji Matsushima; Shingo Takada; Arata Fukushima; Wataru Mizushima; Tomoyasu Kadoguchi; Yoshihiro Masaki; Takashi Yokota; Hiroyuki Tsutsui, CIRCULATION, 130, Nov. 2014
  English, Summary international conference
• AST-120 Ameliorates Lowered Exercise Capacity and Mitochondrial Dysfunction of the Skeletal Muscle in Mice with Chronic Kidney Disease via Reducing Oxidative Stress
  Mikito Nishikawa; Naoki Ishimori; Shingo Takada; Akimichi Saito; Tomoyasu Kadoguchi; Takaaki Furihata; Arata Fukushima; Shouji Matsushima; Takashi Yokota; Shintaro Kinugawa; Hiroyuki Tsutsui, CIRCULATION, 130, Nov. 2014
  English, Summary international conference
• Changes of Metabolomic Profiling Are Associated With Reduced Exercise Capacity in Patients With Heart Failure
  Masaya Tsuda; Shintaro Kinugawa; Arata Fukushima; Shoji Matsushima; Takaaki Furihata; Shingo Takada; Tomoyasu Kadoguchi; Masato Kudo; Junichi Matsumoto; Takashi Yokota; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 130, Nov. 2014
  English, Summary international conference
• Brain-Derived Neurotrophic Factor Maintains Exercise Capacity and Mitochondrial Function in the Skeletal Muscle Through Ampk-Pgc1 alpha Signaling
  Shingo Takada; Shintaro Kinugawa; Shouji Matsushima; Wataru Mizushima; Arata Fukushima; Takaaki Furihata; Tomoyasu Kadoguchi; Takashi Yokota; Tadashi Suga; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 130, Nov. 2014
  English, Summary international conference
• Angiotensin II Directly Induces Mitochondrial Dysfunction and Atrophy in the Skeletal Muscle
  Tomoyasu Kadoguchi; Shintaro Kinugawa; Arata Fukushima; Takaaki Furihata; Tadashi Suga; Shingo Takada; Wataru Mizushima; Masato Kudo; Junichi Matsumoto; Masaya Tsuda; Mikito Nishikawa; Takashi Yokota; Shoji Matsushima; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 130, Nov. 2014
  English, Summary international conference
• Serum Brain-derived Neurotrophic Factor Level Predicts Adverse Clinical Outcomes in Patients with Heart Failure
  Masato Kudo; Shintaro Kinugawa; Arata Fukushima; Takashi Yokota; Shouji Matsushima; Takaaki Furihata; Masaya Tsuda; Junichi Matsumoto; Shingo Takada; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 20, 10, S207, S207, Oct. 2014
  English, Summary international conference
• Angiotensin II Could Directly Induced Mitochondrial Dysfunction and Atrophy in the Skeletal Muscle
  Tomoyasu Kadoguchi; Shintaro Kinugawa; Arata Fukushima; Takaaki Furihata; Shingo Takada; Takashi Yokota; Shoji Matsushima; Koichi Okita; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 20, 10, S148, S148, Oct. 2014
  English, Summary international conference
• Impaired Mitochondrial Oxidative Phosphorylation and Fatty Acid Oxidation with Enhanced Mitochondrial Oxidative Stress in Spontaneously-occurring Feline Hypertrophic Cardiomyopathy
  Takashi Yokota; Liselotte B. Christiansen; Flemming Dela, JOURNAL OF CARDIAC FAILURE, 20, 10, S147, S147, Oct. 2014
  English, Summary international conference
• Changes of Metabolomic Profiling are Associated with Reduced Exercise Capacity in Patients with Heart Failure
  Masaya Tsuda; Shintaro Kinugawa; Arata Fukushima; Takashi Yokota; Shoji Matsushima; Takaaki Furihata; Shingo Takada; Masato Kudo; Junichi Matsumoto; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 20, 10, S191, S191, Oct. 2014
  English, Summary international conference
• Sesamin improves lowered exercise capacity and mitochondrial dysfunction in the skeletal muscle from high fat diet-induced diabetic mice
  S. Takada; S. Kinugawa; D. Takemoto; T. Kadoguchi; T. Yokota; S. Matsushima; A. Fukushima; Y. Masaki; T. Furihata; T. Suga; W. Mizushima; Y. Ono; H. Shibata; K. Okita; H. Tsutsui, DIABETOLOGIA, 57, S258, S258, Sep. 2014
  English, Summary international conference
• 本学での子宮頸がんワクチン接種実施報告 不安と疼痛の影響から考えられたこと
  川原 由佳子; 折戸 智恵子; 吉村 彩; 石原 可愛; 大西 俊介; 横田 卓; 橋野 聡, 全国大学保健管理研究集会プログラム・抄録集, 52回, 58, 58, Aug. 2014
  (公社)全国大学保健管理協会, Japanese
• 動物実験従事者におけるアレルギー健診3年分の経年的解析
  吉村 彩; 折戸 智恵子; 川原 由佳子; 横田 卓; 大西 俊介; 橋野 聡, 全国大学保健管理研究集会プログラム・抄録集, 52回, 103, 103, Aug. 2014
  (公社)全国大学保健管理協会, Japanese
• Dipeptidyl Peptidase-4 Inhibitor Improved Exercise Capacity in Association with Switching to Oxidative Skeletal Muscle Fiber Type in Mice with Post-infarct Heart Failure
  Yoshihiro Masaki; Shintaro Kinugawa; Shingo Takada; Tomoyasu Kadoguchi; Arata Fukushima; Tsuneaki Homma; Takaaki Furihata; Ryoichi Katsuyama; Tadashi Suga; Masashige Takahashi; Takashi Yokota; Shouji Matsushima; Koichi Okita; Hiroyuki Tsutsui, DIABETES, 63, A479, A479, Jun. 2014
  English, Summary international conference
• 定期健康診断の血圧測定における本学の取り組み 高血圧の偽陽性の学生を少なくするために
  川原 由佳子; 谷 忍; 小西 剛; 折戸 智恵子; 吉村 彩; 横田 卓; 渡辺 昌也; 大西 俊介; 橋野 聡, CAMPUS HEALTH, 51, 1, 268, 270, Mar. 2014
  (公社)全国大学保健管理協会, Japanese
• 留学生の尿検査有所見の傾向 陽性率からみる健診対策
  吉村 彩; 折戸 智恵子; 川原 由佳子; 小西 剛; 谷 忍; 前野 由紀子; 渡邉 昌也; 横田 卓; 大西 俊介; 橋野 聡, CAMPUS HEALTH, 51, 1, 297, 299, Mar. 2014
  定期健康診断時(定健)の尿検査や再検査の結果について、一般学生(日本国籍)と比較し、留学生における尿検査有所見の傾向について検討した。定健尿検査を受診した学生31555例を一般学生と留学生に分けて検討した。定健尿検査(1回目)の再検該当者は、一般学生は平均3.2%であったが、留学生平均7.7%と高かった。さらに、男女別では、女性の留学生に高い傾向が見られた。再検該当項目別の陽性率は、尿潜血賜性は留学生及び男女、特に女性で高かった。再検受診者のうち、他医療機関へ紹介した紹介率は、留学生が平均5割と高いが、医療機閣からの返信が来た返信率は、一般学生の方が高かった。医療機関からの返信内容では、異常なしと血尿が多い傾向にあった。留学生の受診者数でもっとも多いのがアジアで、再検該当率、受診率最多は中国で次いで韓国、インドネシアに多く多かった。, (公社)全国大学保健管理協会, Japanese
• 一酸化窒素は運動誘発性の運動能力と骨格筋ミトコンドリア増加を調節する
  門口 智泰; 絹川 真太郎; 菅 唯志; 小野 太祐; 横田 卓; 高田 真吾; モハマド・アリ・ソビリン; 高橋 将成; 福島 新; 本間 恒章; 正木 芳宏; 平林 鑑; 沖田 孝一; 筒井 裕之, 心臓リハビリテーション, 19, 1, 138, 142, Feb. 2014
  (NPO)日本心臓リハビリテーション学会, Japanese
• 解離性総肝動脈瘤・脾動脈瘤を合併したStanford B型大動脈解離の一例
  松谷健一; 片山貴史; 神谷究; 松島将士; 横田卓; 榊原守; 筒井裕之, 日本循環器学会北海道地方会(Web), 112th, 2014
• デバイス関連感染性心内膜炎に対しエキシマレーザーによる経静脈的リード抜去が奏効した一例
  徳田裕輔; 鎌田塁; 神谷究; 松島将士; 横田卓; 榊原守; 四倉昭彦; 筒井裕之, 日本循環器学会北海道地方会(Web), 112th, 2014
• 厚生労働省による積極的勧奨中止後に子宮頸がんワクチン接種を受けた大学生への意識調査
  川原 由佳子; 齋藤 暢一朗; 大西 俊介; 吉村 彩; 石原 可愛; 横田 卓; 橋野 聡, 日本看護学会論文集. ヘルスプロモーション, 45, 89, 92, 2014
  日本看護学会 ; 2015-, Japanese
• Decreased Serum Brain-Derived Neurotrophic Factor Levels are Associated With Exercise Intolerance in Patients With Heart Failure
  Shingo Takada; Shintaro Kinugawa; Arata Fukushima; Tsuneaki Homma; Yoshihiro Masaki; Takaaki Furihata; Ryoichi Katsuyama; Takashi Yokota; Shouji Matsushima; Takahiro Abe; Tadashi Suga; Tomoyasu Kadoguchi; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 128, 22, Nov. 2013
  English, Summary international conference
• Serum Myostatin Levels Are Independent Determinant of Skeletal Muscle Wasting in Patients With Heart Failure
  Takaaki Furihata; Shintaro Kinugawa; Arata Fukushima; Tsuneaki Homma; Yoshihiro Masaki; Takahiro Abe; Shingo Takada; Tomoyasu Kadoguchi; Koichi Okita; Shouji Matsushima; Takashi Yokota; Hiroyuki Tsutsui, CIRCULATION, 128, 22, Nov. 2013
  English, Summary international conference
• Resitance exercise with blood flow restriction in women
  K. Okita; S. Takada; T. Suga; T. Kadoguchi; T. Taniura; N. Morita; T. Yokota; S. Kinugawa; H. Tsutsui, 13TH AFSM PROCEEDINGS, 73, 75, 2013, [Invited]
  English, Introduction scientific journal
• 冠動脈攣縮を有する患者において, 睡眠呼吸障害は, 心臓突然死の独立した危険因子である
  榊原 守; 山田 史郎; 神谷 究; 横田 卓; 筒井 裕之; 大庭 幸治, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 88, 1, 32, 32, 01 Jan. 2013
  Japanese
• A case of Paget-Schroetter syndrome, or effort thrombosis of axillary-subclavial vein
  Aikawa Tadao; Ishimori Naoki; Mizushima Wataru; Mizukami Kazuya; Hamaguchi Sanae; Yokota Takashi; Sakakibara Mamoru; Furumoto Tomoo; Kubota Suguru; Matsui Yoshiro; Tsutsui Hiroyuki; Kikuchi Seiya, Shinzo, 44, 10, 1275, 1279, Oct. 2012
  症例は，30歳代，男性．生来健康．前医初診2週間前より軽度の左上肢浮腫を自覚していたが，スキー後に急に左上肢の浮腫が増悪し，熱感も伴ったため，翌日前医を初診．画像所見から左鎖骨下静脈血栓症と診断され，抗凝固療法を導入した．その後症状改善したが，3週間後に安静時胸部不快感を自覚し，肺血栓塞栓症の合併が疑われて当院に入院するも，その後の経過より同症の合併は否定された．血液検査で血栓性素因は認めず，コンピュータ断層撮影(computerized tomography；CT)，磁気共鳴像(magnetic resonance imaging；MRI)などの画像検査で左鎖骨下静脈の圧排所見も認めないことより，パジェット・シュロッター症候群(Paget-Schroetter syndrome；PSS)と診断した．本症候群は，鎖骨と第1肋骨間の空隙が上肢の動きで狭小化し，鎖骨下静脈が慢性的に機械的刺激を受けて局所で血栓形成されると考えられており，比較的，稀な症例と考えられたために報告する．, Japan Heart Foundation, Japanese
• 体外式補助人工心臓装着患者に対する心臓リハビリテーションの経験
  阿部隆宏; 堀享一; 横田卓; 絹川真太郎; 後藤大祐; 大岡智学; 久保田卓; 松居喜郎; 筒井裕之; 生駒一憲, 北海道リハビリテーション学会雑誌, 37, 49-52, 52, 30 May 2012
  北海道リハビリテーション学会, Japanese
• 冠動脈硬化性疾患の病態の把握及び早期診断のための血漿プラスマローゲンの有用性に関しての検討
  西向めぐみ; 榊原守; 横田卓; 山田史郎; 櫻井俊宏; 高橋祐司; 生田知子; 古牧宏啓; 山木志展; 前場良太; 千葉仁志; 筒井裕之; 原博, 日本栄養・食糧学会大会講演要旨集, 66th, 154, 27 Apr. 2012
  Japanese
• Oxidative stress impairs insulin signal in skeletal muscle and causes insulin resistance in postinfarct heart failure
  太田 幸博; 絹川 真太郎; 松島 将士; 小野 太祐; アリ ソビリン; 井上 直樹; 横田 卓; 平林 鑑; 筒井 裕之, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 2, 69, 69, 01 Apr. 2012
  Japanese
• 酸化ストレスと心不全患者における骨格筋異常
  高田 真吾; 絹川 真太郎; 平林 鑑; 横田 卓; 菅 唯志; 高橋 将成; 福島 新; 本間 恒章; 正木 芳宏; 門口 智泰; 佐藤 貴志; 森田 憲輝; 堀内 雅弘; 沖田 孝一; 筒井 裕之, 心臓リハビリテーション, 17, 1, 139, 142, Feb. 2012
  (NPO)日本心臓リハビリテーション学会, Japanese
• ピオグリタゾンはインスリン抵抗性患者の骨格筋エネルギー代謝を改善し有酸素運動能を増加させる
  高橋 将成; 絹川 真太郎; 横田 卓; 平林 鑑; 高田 真吾; 菅 唯志; 福島 新; 本間 恒章; 正木 芳宏; 門口 智泰; 佐藤 貴志; 沖田 孝一; 筒井 裕之, 心臓リハビリテーション, 17, 1, 155, 158, Feb. 2012
  (NPO)日本心臓リハビリテーション学会, Japanese
• Resistance Training with Blood Flow Restriction: Adjusting the Method for Gender Difference
  沖田孝一; 吉田真; 森田憲輝; 横田卓; 堀内雅弘, デサントスポーツ科学, 33, 2012
• Effects of Aerobic Capacity on Intramuscular Metabolism and Oxygen Kinetics during Resistance Exercise with Blood Flow Restriction
  高田真吾; 高田真吾; 沖田孝一; 沖田孝一; 菅唯志; 菅唯志; 堀内雅弘; 佐古隆之; 森田憲輝; 面川雅司; 門口智泰; 佐藤貴志; 高橋将成; 福島新; 本間恒章; 正木芳宏; 横田卓; 絹川真太郎; 筒井裕之, 脈管学(Web), 52, April, 2012
• 血流制限を併用した筋力トレーニングの効果 女性における至適方法の検討へ
  沖田 孝一; 絹川 真太郎; 横田 卓; 森田 憲輝; 佐々木 浩子, 女性健康科学研究会受賞研究報告集, 1, 4, 8, Jan. 2012
  女性および男性における血流制限を併用したレジスタンス運動の効果を単回運動時の筋内代謝的ストレスから評価し、その差異について検討した。仰臥位における右足関節底屈運動を毎分30回のペースで、総計60回(2分間)施行した。女性の最大挙上重(1-RM)は男性に比べて有意に低かったため、各条件における絶対的負荷量は、女性において低値となった。また、収縮期血圧も女性において低値であったため血流制限圧も低くなった。安静から運動時における骨格筋内クレアチンリン酸は、各条件・時間において、男女間の有意差は見られなかった。65%1-RM条件において、女性における筋細胞内pHの低下が小さいように見えるが、クレアチンリン酸同様に各条件・時間においても男女間の有意差はみられなかった。男性、女性同様に血流制限により有意にクレアチンリン酸、筋細胞内pHの低下は増強したが、高強度負荷には及んでいなかった。, 女性健康科学研究会, Japanese
• 血液生化学的にみた運動療法の効果:脳機能を反映する新指標の可能性
  沖田 孝一; 森田 憲輝; 横田 卓; 村上 猛; 佐々木 浩子; 絹川 真太郎, 北翔大学北方圏学術情報センター年報, 4, 71, 74, 2012
  北翔大学, Japanese
• 一酸化窒素は運動トレーニング誘発性の運動能力と骨格筋ミトコンドリア機能の増加を調節する
  門口智泰; 絹川真太郎; 菅唯志; 小野太祐; 高田真吾; モハマド アリソビリン; 高橋将成; 福島新; 本間恒章; 横田卓; 平林鑑; 沖田孝一; 筒井裕之, 日本心臓リハビリテーション学会学術集会プログラム抄録集(Web), 18th, O-190 (WEB ONLY), 2012
  Japanese
• Effects of Aerobic Capacity on Intramuscular Metabolism and Oxygen Kinetics during Resistance Exercise with Blood Flow Restriction
  Takada Shingo; Takahashi Masashige; Fukushima Arata; Homma Tsuneaki; Masaki Yoshihiro; Yokota Takashi; Kinugawa Shintaro; Tsutsui Hiroyuki; Okita Koichi; Suga Tadashi; Horiuchi Masahiro; Sako Takayuki; Morita Noriteru; Omokawa Masashi; Kadoguchi Tomoyasu; Sato Takashi, The Journal of Japanese College of Angiology, 52, 0, 217, 222, 2012
  Blood flow restriction (BFR) remarkably enhances intramuscular energetic metabolism in resistance exercise; however, its mechanism has not been known. We hypothesized that it was associated with oxidative capacity. Therefore, we investigated intramuscular metabolic responses during low-intensity resistance exercise with BFR in track athletes. Twelve male college athletes were recruited and performed unilateral plantar-flexion (30 repetitions/minute for 2 minutes) during low-intensity exercise at 20% of one repetition maximum with BFR. Intramuscular energetic metabolism and muscle oxygenation were evaluated using ³¹P-magnetic resonance spectroscopy and near infrared spectroscopy, respectively. Subjects were divided into the two groups based on aerobic capacity. Phosphocreatine (PCr) decrease in subjects with high-aerobic capacity during BFR exercise was greater than that in subjects with low-aerobic capacity (p=0.077), without the difference in muscular oxygenation. The PCr decrease during BFR exercise was significantly correlated with peak oxygen uptake (r=0.735, p<0.01). In conclusion, the effects of low-intensity resistance exercise with BFR might be greater in subjects with higher aerobic capacity., Japanese College of Angiology, Japanese
• The Disruption of Natural Killer T Cell Exacerbates Cardiac Hypertrophy and Heart Failure Due to Pressure Overload in Mice
  Masashige Takahashi; Arata Fukushima; Tsuneaki Homma; Mochamad A. Sobirin; Tadashi Suga; Shingo Takada; Taisuke Ono; Yoshihiro Masaki; Tomoyasu Kadoguchi; Takashi Yokota; Shintaro Kinugawa; Hiroyuki Tsutsui, CIRCULATION, 124, 21, Nov. 2011
  English, Summary international conference
• Direct Renin Inhibitor Ameliorates Insulin Resistance by Improving Insulin Signaling in the Skeletal Muscle in Experimental Post-Infarct Heart Failure
  Arata Fukushima; Shintaro Kinugawa; Takashi Yokota; Sobrin A. Mochamad; Masashige Takahashi; Tsuneaki Homma; Tadashi Suga; Shingo Takada; Yoshihiro Masaki; Tomoyasu Kadoguchi; Kouichi Okita; Hiroyuki Tsutsui, CIRCULATION, 124, 21, Nov. 2011
  English, Summary international conference
• Nitric Oxide is Involved the Beneficial Effects of Exercise Training via Activating Skeletal Muscle Mitochondrial Biogenesis in Mice
  Tadashi Suga; Shintaro Kinugawa; Taisuke Ono; Takashi Yokota; Shingo Takada; Mochamad A. Sobirin; Masashige Takahashi; Arata Fukushima; Tsuneaki Homma; Tomoyasu Kadoguchi; Yoshihiro Masaki; Kagami Hirabayashi; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 124, 21, Nov. 2011
  English, Summary international conference
• Enhanced Oxidative Stress is Correlated With Skeletal Muscle Abnormalities in Patients With Metabolic Syndrome
  Shintaro Kinugawa; Takashi Yokota; Kagami Hirabayashi; Tadashi Suga; Masashige Takahashi; Shingo Takada; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 124, 21, Nov. 2011
  English, Summary international conference
• The Disruption of Natural Killer T Cell Receptor Exacerbates Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice
  Masashige Takahashi; Arata Fukushima; Tsuneaki Homma; Mochamad A. Sobirin; Tadashi Suga; Shingo Takada; Tomoyasu Kadoguchi; Yoshihiro Masaki; Takashi Yokota; Shintaro Kinugawa; Hiroyuki Tsutsui, CIRCULATION, 124, 21, Nov. 2011
  English, Summary international conference
• The Activation of Natural Killer T Cells Ameliorates Myocardial Ischemia Reperfusion Injury in Mice
  Tsuneaki Homma; Shintaro Kinugawa; Takashi Yokota; Masashige Takahashi; Arata Fukushima; Tadashi Suga; Shingo Takada; Yoshihiro Masaki; Tomoyasu Kadoguchi; Taisuke Ono; Mochamad A. Sobirin; Hiroyuki Tsutsui, CIRCULATION, 124, 21, Nov. 2011
  English, Summary international conference
• Angiotensin II Receptor Blocker Improves Exercise Capacity and Mitochondrial Function of Skeletal Muscle via Inhibiting Oxidative Stress in High Fat Diet-Induced Diabetic Mice
  Shingo Takada; Shintaro Kinugawa; Takashi Yokota; Tadashi Suga; Masashige Takahashi; Arata Fukushima; Tsuneaki Homma; Sobirin A. Mochamad; Taisuke Ono; Yoshihiro Masaki; Tomoyasu Kadoguchi; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 124, 21, Nov. 2011
  English, Summary international conference
• The Enhanced Oxidative Stress is Associated with Skeletal Muscle Abnormalities in Patients with Heart Failure
  Shintaro Kinugawa; Kagami Hirabayashi; Tadashi Suga; Masashige Takahashi; Shingo Takada; Takashi Yokota; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 124, 21, Nov. 2011
  English, Summary international conference
• The Activation of Natural Killer T Cells Ameliorates Myocardial Ischemia Reperfusion Injury in Mice
  Tsuneaki Homma; Shintaro Kinugawa; Takashi Yokota; Masashige Takahashi; Arata Fukushima; Tadashi Suga; Shingo Takada; Yoshihiro Masaki; Tomoyasu Kadoguchi; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 17, 9, S153, S153, Sep. 2011
  English, Summary international conference
• Direct Renin Inhibitor (Aliskiren) Improves Insulin Resistance and Impaired Insulin Signal in Post-Infarct Heart Failure
  Arata Fukushima; Shintaro Kinugawa; Takashi Yokota; Masashige Takahashi; Tsuneaki Homma; Tadashi Suga; Shingo Takada; Yoshihiro Masaki; Tomoyasu Kadoguchi; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 17, 9, S152, S152, Sep. 2011
  English, Summary international conference
• New aspects of guidelines for treatment of chronic heart failure (JCS 2010)
  Yokota T, Tsutsui H, Nihon Rinsho, 69, 9, 1691, 1697, Sep. 2011, [Invited], [Lead author]
  日本臨床社, Japanese, Introduction scientific journal
• The activation of natural killer T cells ameliorates post-infarct heart failure in mice
  M. A. Sobirin; S. Kinugawa; M. Takahashi; T. Ono; A. Fukushima; T. Yokota; T. Homma; N. Ishimori; K. Iwabuchi; H. Tsutsui, EUROPEAN HEART JOURNAL, 32, 663, 664, Aug. 2011
  English, Summary international conference
• 運動による健康増進の科学最前線
  沖田 孝一,森田 憲輝,横田 卓,村上 猛,佐々木 浩子,絹川 真太郎, 北翔大学北方圏学術情報センター年報, 3, 119, 122, Mar. 2011
  北翔大学, Japanese, Introduction research institution
• 脳梗塞を発症したLVAD装着患者に対するリハビリテーションの経験
  小島尚子; 堀享一; 阿部隆宏; 榊原守; 後藤大祐; 絹川真太郎; 横田卓, 心臓リハビリテーション, 16, 2 Suppl., 2011
• The activation of natural killer T cells ameliorates post-infarct heart failure in mice
  M. A. Sobirin; S. Kinugawa; M. Takahashi; T. Ono; A. Fukushima; T. Yokota; T. Homma; N. Ishimori; K. Iwabuchi; H. Tsutsui, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 183, 663, 664, 2011
  English, Summary international conference
• 酸化ストレス亢進は心不全患者における骨格筋異常に関連する
  高田真吾; 絹川真太郎; 平林鑑; 横田卓; 菅唯志; 森田憲輝; 小野太祐; ソビリン モハマドアリ; 高橋将成; 福島新; 本間恒章; 沖田孝一; 筒井裕之, 心臓リハビリテーション, 16, 2 Suppl., S152, 2011
  Japanese
• 食事療法と運動療法の併用は,糖尿病マウスの運動能力と骨格筋ミトコンドリア機能を正常化する
  菅唯志; 絹川真太郎; 高田真吾; 高橋将成; 福島新; 本間恒章; アリ ソビリン; 小野太祐; 横田卓; 沖田孝一; 筒井裕之, 心臓リハビリテーション, 16, 2 Suppl., S229, 2011
  Japanese
• ピオグリタゾンはインスリン抵抗性患者の高エネルギーリン酸代謝を改善し有酸素運動能を増加させる
  高橋将成; 絹川真太郎; 横田卓; 高田真吾; 福島新; 菅唯志; 佐藤貴志; 門口智泰; 沖田孝一; 筒井裕之, 心臓リハビリテーション, 16, 2 Suppl., S153, 2011
  Japanese
• 個体内四肢における骨格筋機能と血流依存性血管拡張反応
  門口智泰; 沖田孝一; 菅唯志; 高田真吾; 佐藤貴志; 森田憲輝; 堀内雅弘; 高橋将成; 福島新; 横田卓; 平林鑑; 絹川真太郎; 筒井裕之, 心臓リハビリテーション, 16, 2 Suppl., S165, 2011
  Japanese
• 単回の血流制限を併用したレジスタンストレーニングが動脈硬化指標へ与える影響
  佐藤貴志; 沖田孝一; 菅唯志; 高田真吾; 門口智泰; 森田憲輝; 堀内雅弘; 高橋将成; 福島新; 横田卓; 平林鑑; 絹川真太郎; 筒井裕之, 心臓リハビリテーション, 16, 2 Suppl., S250, 2011
  Japanese
• Discharge Use of Spironolactone was Associated with Lower Long-term Mortality in Patients Hospitalized with Systolic Heart Failure
  Sanae Hamaguchi; Shintaro Kinugawa; Takashi Yokota; Miyuki Tsuchihashi-Makaya; Hiroyuki Tsutsui, CIRCULATION, 122, 21, Nov. 2010
  English, Summary international conference
• The Disruption of Natural Killer T Cell Receptor Exacerbates Post-Infarct Heart Failure in Mice
  Mochamad Ali Sobirin; Shintaro Kinugawa; Taisuke Ono; Kagami Hirabayashi; Tadashi Suga; Takashi Yokota; Naoki Ishimori; Kazuya Iwabuchi; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 16, 9, S164, S164, Sep. 2010
  English, Summary international conference
• Pioglitazone increases the aerobic capacity with improved skeletal muscle energetics in patients with insulin resistance
  T. Yokota; S. Kinugawa; K. Hirabayashi; T. Suga; S. Takada; M. Takahashi; S. A. Mochamad; T. Ono; N. Morita; K. Okita; H. Tsutsui, DIABETOLOGIA, 53, Sep. 2010
  English, Summary international conference
• Cardiac Remodeling and Diastolic Dysfunction in DahlS.Z-Lepr(fa)/Lepr(fa) Rats as a New Rat Model of Metabolic Syndrome
  Mamoru Sakakibara; Sirou Yamada; Takashi Yokota; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 16, 9, S147, S148, Sep. 2010
  English, Summary international conference
• The Effect on Intramuscular Metabolic Stress During Low-Intensity Resistance Exercise With Blood Flow Restriction in Patients With Heart Failure
  Masashige Takahashi; Shintaro Kinugawa; Shingo Takada; Tadashi Suga; Arata Fukushima; Tomoyasu Kadoguchi; Kagami Hirabayashi; Takashi Yokota; Koichi Okita; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 16, 9, S162, S162, Sep. 2010
  English, Summary international conference
• The Activation of Natural Killer T Cells Ameliorates Post-Infarct Heart Failure in Mice
  Mochamad Ali Sobirin; Shintaro Kinugawa; Taisuke Ono; Kagami Hirabayashi; Tadashi Suga; Takashi Yokota; Naoki Ishimori; Kazuya Iwabuchi; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 16, 8, S31, S31, Aug. 2010
  English, Summary international conference
• 疾患の理解編 (疾患と看護がわかる看護過程 ナーシングプロセス 心不全)
  横田 卓; 筒井 裕之, クリニカルスタディ, 31, 8, 686, 692, Jul. 2010
  メヂカルフレンド社, Japanese
• 血流制限を併用した短期間の低強度筋力トレーニングが筋量・筋力および動脈硬化指標に与える影響
  門口智泰; 沖田孝一; 菅唯志; 高田真吾; 面川雅司; 佐藤貴志; 今泉貴; 森田憲輝; 高橋将成; 横田卓; 平林鑑; 絹川真太郎; 筒井裕之, 心臓リハビリテーション, 15, Suppl., S256, 15 Jun. 2010
  Japanese
• 慢性心不全に対する運動療法の継続に及ぼす患者背景因子の検討
  後藤大祐; 堀享一; 絹川真太郎; 横田卓; 小島尚子; 筒井裕之, 心臓リハビリテーション, 15, Suppl., S180, 15 Jun. 2010
  Japanese
• 血行動態から診た難治性心不全
  横田 卓; 筒井 裕之, Heart View, 14, 6, Jun. 2010, [Invited], [Lead author]
  Japanese, Introduction scientific journal
• High-metabolic Stress During Resistance Exercise Might Provide Muscle Hypertrophy And Strength Increase Even With Low-mechanical Stimulus
  Shingo Takada; Koichi Okita; Tadashi Suga; Masashi Omokawa; Tomoyasu Kadoguchi; Noriteru Morita; Masahiro Horiuchi; Masashige Takahashi; Takashi Yokota; Kagami Hirabayashi; Shintaro Kinugawa; Hiroyuki Tsutsui, MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, 42, 5, 498, 498, May 2010
  English, Summary international conference
• Difference In Metabolic Stress During Resistance Exercise With Blood Flow Restriction Between Sprinters And Endurance Runners
  Tomoyasu Kadoguchi; Koichi Okita; Tadashi Suga; Shingo Takada; Masashi Omokawa; Noriteru Morita; Masahiro Horiuchi; Masashige Takahashi; Takashi Yokota; Kagami Hirabayashi; Shintaro Kinugawa; Hiroyuki Tsutsui, MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, 42, 5, 41, 41, May 2010
  English, Summary international conference
• Myocardial ischemia and metabolic disorder
  Yokota T, Kinugawa S, Tsutsui H, Nihon Rinsho, 68, 621, 624, Apr. 2010, [Invited], [Lead author]
  Japanese, Introduction scientific journal
• 心不全
  横田 卓; 筒井 裕之, Clinical Study (メジカルフレンド社), 31, 6, 12, 2010, [Invited], [Lead author]
  Japanese, Introduction scientific journal
• 高血圧心疾患
  横田 卓; 筒井 裕之, 診療に活かす心機能評価 (羊土社出版; 北風 政史編), 200, 204, 2010, [Invited], [Lead author]
  Japanese, Introduction scientific journal
• ミトコンドリア (エネルギーの産生)
  横田 卓; 筒井 裕之, 診療に活かす心機能評価 (羊土社出版; 北風 政史編), 26, 29, 2010, [Invited], [Lead author]
  Japanese, Introduction scientific journal
• Characteristics and Outcomes of Hospitalized Patients With Heart Failure and Reduced vs Preserved Ejection Fraction - A Report From the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) (vol 73, pg 1893, 2009)
  Miyuki Tsuchihashi-Makaya; Sanae Hamaguchi; Shintaro Kinugawa; Takashi Yokota; Daisuke Goto; Hisashi Yokoshiki; Norihiro Kato; Akira Takeshita; Hiroyuki Tsutsui, CIRCULATION JOURNAL, 73, 12, 2365, 2365, Dec. 2009
  English, Others
• Pioglitazone Improves Aerobic Capacity and Skeletal Muscle High-Energy Phosphate Metabolism in Patients With Metabolic Syndrome
  Takashi Yokota; Shintaro Kinugawa; Kagami Hirabayashi; Tadashi Suga; Noriteru Morita; Masahige Takahashi; Shingo Takada; Masashi Omokawa; Shouji Matsushima; Mochamad A. Sobirin; Taisuke Ono; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 120, 18, S550, S550, Nov. 2009
  English, Summary international conference
• The Increase in Intramyocellular Lipid in Leg Skeletal Muscle is Associated With Lowered Aerobic Exercise Capacity in Patients With Heart Failure
  Kagami Hirabayashi; Shintaro Kinugawa; Takashi Yokota; Tadashi Suga; Noriteru Morita; Taisuke Ono; Mochamad A. Sobirin; Masashige Takahashi; Koichi Okita; Hiroyuki Tsutsui, CIRCULATION, 120, 18, S550, S550, Nov. 2009
  English, Summary international conference
• The Increase in Intramyocellular Lipid in Leg Skeletal Muscle is Associated With Lowered Aerobic Exercise Capacity in Heart Failure Patients
  Kagami Hirabayashi; Shintaro Kinugawa; Takashi Yokota; Tadashi Suga; Noriteru Morita; Taisuke Ono; Mochamad Ali Sobirin; Masashige Takahashi; Koichi Okita; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 15, 7, S165, S165, Sep. 2009
  English, Summary international conference
• The Activation of Natural Killer T Cells Ameliorates Post-Infarct Heart Failure in Mice
  Mochamad Ali Sobirin; Shintaro Kinugawa; Taisuke Ono; Kagami Hirabayashi; Tadashi Suga; Takashi Yokota; Naoki Ishimori; Kazuya Iwabuchi; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 15, 7, S151, S151, Sep. 2009
  English, Summary international conference
• OJ-191 Remarkable Effects of Continuous Blood Flow Restriction during Multiple Sets of Low Intensity Resistance Exercise(OJ32,Exercise Test/Cardiac Rehabilitation (H),Oral Presentation (Japanese),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)
  Suga Tadashi; Okita Koichi; Morita Noriteru; Takada Singo; Omokawa Masashi; Horiuchi Masahiro; Yokota Takashi; Hirabayashi Kagami; Kinugawa Shintaro; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 73, 334, 334, 01 Mar. 2009
  Japanese Circulation Society, English
• PJ-026 Pravastatin Ameliorates the Development of High Fat Diet-induced Diabetes by Inhibiting Oxidative Stress and Insulin Signaling Defects in Skeletal Muscle(PJ005,Diabetes 1 (H),Poster Session (Japanese),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)
  Ono Taisuke; Kinugawa Shintaro; Matusima Syouji; Ohta Yukihiro; Yokota Takashi; Hirabayashi Kagami; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 73, 552, 552, 01 Mar. 2009
  Japanese Circulation Society, English
• OE-259 Lowered Aerobic Exercise Capacity was Associated with Impaired Skeletal Muscle Energy Metabolism in Patients with Metabolic Syndrome(OE44,Exercise Test/Cardiac Rehabilitation (H),Oral Presentation (English),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)
  Yokota Takashi; Kinugawa Shintaro; Hirabayashi Kagami; Inoue Naoki; Ohta Yukihiro; Ono Taisuke; Matusima Syouji; Okita Koichi; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 73, 240, 240, 01 Mar. 2009
  Japanese Circulation Society, English
• PJ-309 Angiotensin II Impairs Skeletal Muscle Properties and Limits Exercise Capacity(PJ052,Hypertension, Basic (H),Poster Session (Japanese),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)
  Hirabayashi Kagami; Kinugawa Shintaro; Inoue Naoki; Yokota Takashi; Ono Taisuke; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 73, 623, 623, 01 Mar. 2009
  Japanese Circulation Society, English
• 血流制限下低強度レジスタンス運動における性差の検討
  菅唯志; 沖田孝一; 森田憲輝; 高田真吾; 面川雅司; 堀内雅弘; 平林鑑; 横田卓; 絹川真太郎; 筒井裕之, 心臓リハビリテーション, 14, Suppl., 2009
• 左心不全の病態生理
  横田 卓; 絹川真太郎; 筒井裕之, 重症心不全の予防と治療 (中外医学社出版; 北風政史編), 165, 171, 2009, [Invited]
  Japanese, Introduction scientific journal
• INTRAMUSCULAR MUSCULAR METABOLIC LOAD IN MULTIPLE SETS LOW-INTENSITY RESISTANCE EXERCISE WITH DIFFERENT PATTERS OF BLOOD FLOW RESTRICTION
  Shingo Takada; Koichi Okita; Tadashi Suga; Noriteru Morita; Masashi Omokawa; Masahiro Horiuchi; Takashi Yokota; Kagami Hirabayashi; Shintaro Kinugawa; Hiroyuki Tsutsui, JOURNAL OF PHYSIOLOGICAL SCIENCES, 59, 219, 219, 2009
  English, Summary international conference
• EXAMINING A PROTOCOL OF LOW INTENSITY RESISTANCE TRAINING WITH BLOOD FLOW RESTRICTION
  Masashi Omokawa; Koichi Okita; Tadashi Suga; Noriteru Morita; Shingo Takada; Masahiro Horiuchi; Takashi Yokota; Kagami Hirabayashi; Shintaro Kinugawa; Hiroyuki Tsutsui, JOURNAL OF PHYSIOLOGICAL SCIENCES, 59, 220, 220, 2009
  English, Summary international conference
• Basic examinations in low-intensity resistance exercise with blood flow restriction
  沖田 孝一; 菅 唯志; 森田 憲輝; 横田 卓; 平林 鑑; 堀内 雅弘; 高田 真吾; 面川 雅司; 佐々木 浩子; 絹川 真太郎; 筒井 裕之, Bulletin of Hokusho University School of Lifelong Learning Support Systems, 9, 9, 11, 16, 2009
  Hokusho University, Japanese
• 血流制限を併用した低強度レジスタンス運動時の骨格筋の代謝的負荷 : 単回および複数セットからなるプロトコールに関する検討
  高田 真吾; 筒井 裕之; 森田 憲輝; 面川 雅司; 門口 智泰; 堀内 雅弘; 沖田 孝一; 菅 唯志; 平林 鑑; 横田 卓; 絹川 真太郎, 心臓, 41, 2, S2_15, S2_15, 2009
  公益財団法人 日本心臓財団, Japanese
• メタボリック症候群では骨格筋エネルギー代謝異常が有酸素運動能を低下させる
  横田 卓; 森田 憲輝; 沖田 孝一; 筒井 裕之; 絹川 真太郎; 平林 鑑; 菅 唯志; 濱口 早苗; 小野 太祐; ソビリン モハマドアリ; 高田 真吾; 面川 雅司, 心臓, 41, 2, S2_17, S2_, 2009
  公益財団法人 日本心臓財団, Japanese
• 2型糖尿病モデルマウスでは, 骨格筋酸化ストレスがミトコンドリア機能を障害し, 運動能力を低下させる
  横田 卓, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 84, 1, 9, 17, 01 Jan. 2009
  Japanese
• Type 2 Diabetes Is Associated with the Exacerbation of Heart Failure via Increasing Myocardial NAD(P)H Oxidase-Derived Superoxide Production
  Shintaro Kinugawa; Shouji Matsushima; Takashi Yokota; Yukihiro Ohta; Naoki Inoue; Hiroyuki Tsutsui, CIRCULATION, 118, 18, S292, S293, Oct. 2008
  English, Summary international conference
• Impaired Skeletal Muscle Energy Metabolism Limits Aerobic Exercise Capacity in Patients with Metabolic Syndrome
  Takashi Yokota; Shintaro Kinugawa; Kagami Hirabayashi; Tadashi Suga; Naoki Inoue; Yukihiro Ohta; Shouji Matsushima; Sanae Hamaguchi; Mochamad A. Sobirin; Taisuke Ono; Noriteru Morita; Kouichi Okita; Hiroyuki Tsutsui, CIRCULATION, 118, 18, S682, S683, Oct. 2008
  English, Summary international conference
• Beta-blocker use at discharge in patients hospitalized for heart failure is associated with improved survival: An analysis from JCARE-CARD
  Miyuki Makaya; Hiroyuki Tsutsui; Sanae Hamaguchi; Shintaro Kinugawa; Takashi Yokota; Daisuke Goto; Akira Takeshita, JOURNAL OF CARDIAC FAILURE, 14, 7, S167, S167, Sep. 2008
  English, Summary international conference
• PJ-907 Oxydative Stress Impairs Mitochondrial Respiration in Skeletal Muscle and Limits Exercise Capacity in Diabetic Mice(Metabolism / Biochemistry / Energetics(03)(M),Poster Session(Japanese),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
  Yokota Takashi; Kinugawa Shintaro; Matsusima Syouji; Inoue Naoki; Ohta Yukihiro; Hirabayashi Kagami; Hamaguchi Sanae; Ono Taisuke; Okita Koichi; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 72, 741, 741, 01 Mar. 2008
  Japanese Circulation Society, English
• OE-372 Angiotensin II-induced Oxidative Stress Impairs Mitochondrial Energy Metabolism in Lower Extremity Skeletal Muscle and Limits Exercise Capacity in Mice(Neurohumoral factors(01)(H),Oral Presentation(English),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
  Inoue Naoki; Kinugawa Shintaro; Yokota Takashi; Ohta Yukihiro; Matusima Syouji; Hamaguchi Sanae; Ono Taisuke; Hirabayashi Kagami; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 72, 273, 273, 01 Mar. 2008
  Japanese Circulation Society, English
• OJ-061 Telmisartan ameliorates insulin resistance by improving insulin signaling in skeletal muscle from mice with heart failure.(Cardiovascular pharmacology, basic/clinical(02)(H),Oral Presentation(Japanese),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
  Ohta Yukihiro; Kinugawa Shintaro; Ono Taisuke; Hirabayashi Kagami; Matusima Syouji; Inoue Naoki; Yokota Takashi; Hamaguchi Sanae; Tsutui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 72, 303, 303, 01 Mar. 2008
  Japanese Circulation Society, English
• OJ-095 Impairment of insulin signaling by oxidative stress in skeletal muscle causes insulin resistance in mice with heart failure.(Heart failure, basic(02)(M),Oral Presentation(Japanese),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
  Ohta Yukihiro; Kinugawa Shintaro; Ono Taisuke; Hirabayashi Kagami; Matsushima Syouji; Inoue Naoki; Yokota Takashi; Hamaguchi Sanae; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 72, 311, 312, 01 Mar. 2008
  Japanese Circulation Society, English
• OJ-145 Optimizing a Protocol of Low Intensity Resistance Training with Blood Flow Restriction(Exercise test / Cardiac rehabilitation(02)(H),Oral Presentation (Japanese),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
  Suga Tadashi; Okita Koichi; Morita Noriteru; Horiuchi Masahiro; Yokota Takashi; Hirabayashi Kagami; Kinugawa Shintaro; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 72, 325, 325, 01 Mar. 2008
  Japanese Circulation Society, English
• 複数セットによる血流制限下低強度レジスタンス運動中の骨格筋代謝的負荷の増加効果
  菅唯志; 沖田孝一; 沖田孝一; 横田卓; 平林鑑; 森田憲輝; 堀内雅弘; 絹川真太郎; 筒井裕之, 心臓リハビリテーション, 13, Suppl., 2008
• 血流制限下低強度レジスタンス運動中の筋内エネルギー代謝
  菅 唯志; 沖田 孝一; 高田 真吾; 高橋 智宏; 面川 雅司; 森田 憲輝; 堀内 雅弘; 平林 鑑; 横田 卓; 絹川 真太郎; 筒井 裕之, 心臓リハビリテーション, 13, 1, 63, 66, Jan. 2008
  磁気共鳴分光法(31P-MRS)を用いて、血流制限下低強度レジスタンス運動中の筋内エネルギー代謝を明らかにし、自然血流下の低強度および高強度レジスタンス運動中と比較検討した。明らかな疾患をもたない健常男性15例を対象とした。被験者の右下腿部下に31P-MRS専用の表面コイルを装着し、右下腿三頭筋の最大筋腹部位を分析対象として行った。低強度負荷条件として、最大挙上重量(1RM)の20%を用いた低強度条件(L)と、血流制限を併用した低強度血流制限条件(LI)、および1RMの65%を用いた高強度条件(H)の3条件による動的足底屈運動を2分間(毎分30回)行い、筋内エネルギー代謝を測定した。LIのクレアチンリン酸および筋内pHの変化は、Lに比較して有意に大きかったが、LIのこれらの変化は、Hに比較して有意に小さかった。, (NPO)日本心臓リハビリテーション学会, Japanese
• 第57回循環器負荷研究会 血流制限下低強度レジスタンス運動中の筋内エネルギー代謝の検討:―血流制限に施行する圧増加の効果―
  菅 唯志; 絹川 真太郎; 筒井 裕之; 沖田 孝一; 高田 真吾; 高橋 智宏; 面川 雅司; 森田 憲輝; 堀内 雅弘; 平林 鑑; 横田 卓, 心臓, 40, 2, 12, 15, 2008
  Japan Heart Foundation, Japanese
• 第57回循環器負荷研究会 糖尿病モデルマウスにおいて骨格筋酸化ストレスが運動能力に与える影響
  横田 卓; 絹川 真太郎; 松島 将士; 井上 直樹; 大田 幸博; 濱口 早苗; ソビリン・; モハメド・アリ; 小野 太祐; 平林 鑑; 沖田 孝一; 筒井 裕之, 心臓, 40, 2, 3, 5, 2008
  公益財団法人 日本心臓財団, Japanese
• 第57回循環器負荷研究会 アンジオテンシンIIは酸化ストレスを増加させることにより直接的に骨格筋のエネルギー代謝を傷害し運動耐容能を低下させる
  井上 直樹; 絹川 真太郎; 横田 卓; 松島 将士; 大田 幸博; 濱口 早苗; ソブリン・モハマド・ アリ; 小野 太祐; 平林 鑑; 筒井 裕之, 心臓, 40, 2, 9, 11, 2008
  公益財団法人 日本心臓財団, Japanese
• PE-426 NAD(P)H Oxidase-derived Oxidative Stress Causes the Exacerbation of Left Ventricular Remodeling and Failure in Diabetes-associated Myocardial Infarction(Heart failure, basic-3, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
  Matusima Syouji; Kinugawa Shintaro; Inoue Naoki; Ohta Yukihiro; Yokota Takashi; Itoh Sanae; Sunagawa Kenji; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 71, 431, 431, 01 Mar. 2007
  Japanese Circulation Society, English
• PJ-120 Exercise Capacity is Limited in Diabetic Mice due to the Impairment of Aerobic Oxidative Capacity in Skeletal Muscle(Metabolism/Biochemistry/Energetics-2, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
  Yokota Takashi; Kinugawa Shintaro; Matusima Syouji; Inoue Naoki; Ohta Yukihiro; Hamaguchi Sanae; Okita Koichi; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 71, 501, 501, 01 Mar. 2007
  Japanese Circulation Society, English
• 第56回 循環器負荷研究会 インスリン抵抗性が運動能力および骨格筋機能に及ぼす影響
  横田 卓; 絹川 真太郎; 松島 将士; 井上 直樹; 大田 幸博; 濱口 早苗; 沖田 孝一; 筒井 裕之, 心臓, 39, 2, 20, 22, 2007
  公益財団法人 日本心臓財団, Japanese
• NAD(P)H oxidase-derived oxidative stress is involved in the exacerbated left ventricular remodeling and failure in diabetes-associated myocardial infarction
  Shouji Matsushima; Shintaro Kinugawa; Naoki Inoue; Yukihiro Ohta; Takashi Yokota; Kenji Sunagawa; Hiroyuki Tsutsui, JOURNAL OF CARDIAC FAILURE, 12, 8, S167, S168, Oct. 2006
  English, Summary international conference
• Current Opinion 不整脈の遺伝子診断
  横田 卓, 蒔田 直昌, 佐々木 孝治, 呼吸と循環, 53, 11, 1187, 1191, Nov. 2005, [Invited], [Lead author]
  医学書院, Japanese, Introduction scientific journal
• 【不整脈における分子機構】 遺伝性不整脈の病態 Brugada症候群とNaチャネル病
  佐々木 孝治, 蒔田 直昌, 横田 卓, 筒井 裕之, 最新医学, 60, 10, 2261, 2266, Oct. 2005, [Invited]
  Japanese, Introduction scientific journal
• Suppressive Effects of the Single Dose of Colestimide on the Postprandial Serum Lipid Levels in Healthy Adult Male Volunteers(Lipid Disorders 1 (H), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
  Nagai Tatsuya; Okita Koichi; Miura Masatake; Yokota Takashi; Tsutsui Hiroyuki, Circulation journal : official journal of the Japanese Circulation Society, 69, 362, 362, 01 Mar. 2005
  Japanese Circulation Society, English
• 第54回循環器負荷研究会 シンポジウム 「加齢と循環器負荷」運動療法が血中高感度CRPに与える影響:閉経前後での反応の違い
  沖田 孝一; 永井 龍哉; 森田 憲輝; 西島 宏隆; 米澤 一也; 三浦 真健; 横田 卓, 心臓, 37, 2, 45, 47, 2005
  公益財団法人 日本心臓財団, Japanese
• 8) 冠動脈拡張症に伴う壁在血栓が末梢塞栓となり生じた急性心筋梗塞(第91回日本循環器学会北海道地方会)
  井上 直樹; 浦澤 一史; 横田 卓; 細谷 昌直; 北畠 顕, Circulation journal : official journal of the Japanese Circulation Society, 68, 0, 864, 864, 20 Oct. 2004
  社団法人日本循環器学会, Japanese
• 23) 経皮的中隔心筋焼灼術(PTSMA)が症状改善に著効を示した1例(第91回日本循環器学会北海道地方会)
  浦澤 一史; 横田 卓; 小室 薫; 小松 博史; 井上 直樹; 山田 聡; 小野塚 久夫; 北畠 顕, Circulation journal : official journal of the Japanese Circulation Society, 68, 0, 865, 865, 20 Oct. 2004
  社団法人日本循環器学会, Japanese
• 47) 混合型結合織病の心病変により多彩な不整脈と右心不全, 低拍出症候群を認め急激な経過にて死亡に至った一例(第90回日本循環器学会北海道地方会)
  丹 通直; 齋藤 晶理; 横田 卓; 大田 幸博; 小松 博史; 長嶋 健一郎; 小野塚 久夫; 米澤 一也; 岡本 洋; 北畠 顕; 天崎 吉晴; 萩原 宏美; 眞木 賀奈子, Circulation journal : official journal of the Japanese Circulation Society, 68, 0, 758, 758, 20 Apr. 2004
  社団法人日本循環器学会, Japanese

• Prevention of lifestyle-related diseases and dementia using polygenic risk scores
  Takashi Yokota
  74th Japanese Society of Internal Medicine Educational Sessions in Hokkaido, 04 Jul. 2026, Japanese, Invited oral presentation
  04 Jul. 2026, [Invited]
• Associations between cardiometabolic risk factors and quantitative peripheral nerve dysfunction in type 2 diabetes
  Takashi Yokota; Naomi Yoshida; Tasuku Inao; Takashi Miyakoshi; Tatsumi Kusakabe; Akira Endoh; Yoichi Ito
  PNS Annual Meeting, 15 Jun. 2026, Peripheral Nerve Society, English
  13 Jun. 2026 - 16 Jun. 2026, Maastricht, Netherlands, [International presentation]
• 非監視型リハビリにおける セルフケアアプリ・IoT機器の活用
  横田 卓
  第3回遠隔心臓リハビリテーション研究会, 16 Apr. 2026, Japanese, Public discourse
  16 Apr. 2026, [Invited]
• “診る”から”支える”へ ～デジタルヘルス・AIが拓く次世代医療～
  横田 卓
  社会保険支払基金北海道支部講演会, 29 Mar. 2026, Japanese, Invited oral presentation
  29 Mar. 2026, [Invited]
• ゲノム情報を活用した次世代型健診 ～ポリジェニックリスクスコア(PRS)による疾病発症リスク予測～
  横田 卓
  令和7年度 日臨技北日本支部「染色体・遺伝子検査部門」研修会, 16 Feb. 2026, Japanese, Public discourse
  16 Feb. 2026 - 28 Feb. 2026, [Invited]
• Cardiac rehabilitation using new devices including IoT and ICT
  Takashi Yokota
  The 44th Annual Meeting of the Japanese Association of Exercise Therapy and Prevention, 13 Sep. 2025, Japanese, Nominated symposium
  13 Sep. 2025 - 14 Sep. 2025, [Invited]
• Use of digital technology in heart failure management and cardiac rehabilitation in Japan
  Takashi Yokota
  AsiaPRevent Expert Lecture, 20 Jul. 2025, The Japanese Association of Cardiac Rehabilitation, English, Nominated symposium
  19 Jul. 2025 - 20 Jul. 2025, Nagoya, Japan, Digital therapeutics is becoming a promising approach to facilitate patient-centered care in prevention and treatment of cardiovascular diseases. There are various digital health tools including mobile apps and wearable sensor devices that can be used for clinical practice. Here I highlight recent advances and current trends of digital and sports cardiology focusing on heart failure management and cardiac rehabilitation in Japan., [Invited], [International presentation]
• これからの心臓リハビリテーションについて
  横田 卓
  Collaborate Web Seminar～多職種で診るこれからの地域医療～, 20 Jun. 2025, Japanese, Public discourse
  20 Jun. 2025, [Invited]
• Prevention of hypertension and antiaging
  Takashi Yokota
  第15回産業保健フォーラムTomorrow, 05 Feb. 2025, Japanese, Invited oral presentation
  [Invited]
• 高血圧・ダイアベティス (糖尿病) とゲノム健診
  横田 卓
  第7回MeCCSフォーラム, 23 Dec. 2024, Japanese, Public discourse
  23 Dec. 2024 - 23 Dec. 2024, [Invited]
• Role of epicardial fat in cardiovascular diseases
  Takashi Yokota
  10th Asian Preventive Cardiology & Cardiac Rehabilitation Conference, 24 Nov. 2024, English, Invited oral presentation
  22 Nov. 2024 - 24 Nov. 2024, [Invited]
• Self-care intervention using mobile application to reduce cardiovascular risks
  Takashi Yokota
  10th Asian Preventive Cardiology & Cardiac Rehabilitation Conference, 23 Nov. 2024, English, Invited oral presentation
  22 Nov. 2024 - 24 Nov. 2024, [Invited]
• 肥満における筋内脂肪蓄積と 運動機能障害
  横田 卓
  第43回日本臨床運動療法学会学術集会, 14 Sep. 2024, Japanese, Nominated symposium
  14 Sep. 2024 - 15 Sep. 2024, [Invited]
• ゲノム情報を活用した次世代型健診: 生活習慣病・認知症
  横田 卓
  第65回日本人間ドック・予防医療学会学術大会, 06 Sep. 2024, Japanese, Public discourse
  06 Sep. 2024 - 07 Sep. 2024, [Invited]
• Self-care intervention using mobile application and IoT devices to reduce cardiovascular risk
  Takashi Yokota
  30th anniversary JACR-EAPC Joint Session, 13 Jul. 2024, English, Nominated symposium
  13 Jul. 2024 - 14 Jul. 2024, [Invited]
• 高血圧症についてもっと知ろう！～予防に取り組む意義とその発症要因～
  横田 卓
  オンラインセミナー, 04 Jun. 2024, Japanese, Public discourse
  04 Jun. 2024, [Invited]
• 試合開始時刻がプロ野球選手の夜間睡眠に及ぼす影響 ―ウェアラブルセンサーを用いた評価―
  宮城和; 松浦倫子; 水島仁; 横田卓; 山仲勇二郎
  日本睡眠学会第45回定期学術集会, 16 Sep. 2023, Japanese, Poster presentation
  15 Sep. 2023 - 17 Sep. 2023
• Brain-derived neurotrophic factor: A key molecule to regulate skeletal muscle function and exercise capacity in heart failure
  Takashi Yokota
  87th Japanese Circulation Society Scientific Sessions (JCS2023), 11 Mar. 2023, English, Nominated symposium
  10 Mar. 2023 - 12 Mar. 2023, [Invited]
• 循環器疾患・糖尿病診療における デジタルヘルスの活用
  横田 卓
  Hokkaido GLP-1 Conference, 07 Jul. 2022, Japanese, Public discourse
  07 Jul. 2022, [Invited]
• Use-case of real world data
  Takashi Yokota
  第9回臨中ネット教育セミナー, 03 Feb. 2022, Japanese, Public discourse
  03 Feb. 2022 - 03 Feb. 2022, [Invited]
• 心臓リハビリテーションとCPX (心肺運動負荷検査)
  横田 卓
  なの花アカデミーサテライト研修会, 16 Nov. 2021, Japanese, Public discourse
  [Invited]
• 新しい医療連携のあり方: 医療連携とデジタルヘルスの活用
  横田 卓
  医療連携を見据えた糖尿病治療～循環器内科から見た糖尿病治療～, 10 Nov. 2021, Japanese, Public discourse
  [Invited]
• Translational research targeting mitochondria: From basic to clinical science
  Takashi Yokota
  The 94th Annual Meeting of the Japanese Biochemical Society, 04 Nov. 2021, English, Nominated symposium
  03 Nov. 2021 - 05 Nov. 2021, [Invited]
• Utilization of real world data (RWD) in hospitals
  Takashi Yokota
  第2回臨中ネット教育セミナー, 14 Jul. 2021, Japanese, Public discourse
  14 Jul. 2021 - 14 Jul. 2021, [Invited]
• 心臓リハビリテーション・ 心肺運動負荷検査 (CPX) の基本と応用
  横田 卓
  第2回恵庭地区心臓リハビリテーションスキルアップセミナー, 05 Mar. 2021, Japanese, Public discourse
  [Invited]
• ICT・IoTを活用した セルフケア強化の取り組み
  横田 卓
  札幌BI LAB ブレインストーミング, 04 Dec. 2020, Japanese, Public discourse
  [Invited]
• 生活習慣の是正を目指したセルフケアアプリの活用
  横田 卓
  第39回日本臨床運動療法学会学術集会, 05 Sep. 2020, Japanese, Nominated symposium
  [Invited]
• IoT・ICTを活用した 心血管病予防
  横田 卓
  第26回日本心臓リハビリテーション学会学術集会, 18 Jul. 2020, Japanese, Nominated symposium
  [Invited]
• 心血管病・生活習慣病における血球ミトコンドリアの バイオマーカーとしての活用の可能性について
  横田 卓
  第5回Cardiac Biomarker研究会, 09 Nov. 2019, Japanese, Invited oral presentation
  [Invited]
• Association of mitochondrial reactive oxygen species generation in circulating blood cells with disease severity and exercise intolerance in patients with chronic heart failure
  Takashi Yokota; Ryosuke Shirakawa; Takayuki Nakajima; Miwako Yamane; Shingo Takada; Shintaro Kinugawa
  ASMRM16 and J-mit19, 04 Oct. 2019, English, Oral presentation
• Application of high-resolution respirometry to mitochondrial research
  Takashi Yokota
  ASMRM16 and J-mit19, 03 Oct. 2019, English, Public discourse
  [Invited]
• Exercise testing and cases
  Takashi Yokota
  IAEA Workshop, 01 Oct. 2019, English, Nominated symposium
  [Invited]
• Role of mitochondria in cardiovascular disease
  Takashi Yokota
  Mitochondrial Physiology 2019 (Copenhagen, Denmark), 23 Aug. 2019, English, Invited oral presentation
  [Invited]
• Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with heart failure
  Takashi Yokota; Shintaro Kinugawa; Hiroyuki Tsutsui
  ACC.19; 68th Annual Scientific Sessions (New Orleans), 18 Mar. 2019, English, Oral presentation
• ICTを活用した 生活習慣病・心血管病の予防
  横田 卓
  日立北大ラボ 産学・地域協働シンポジウム, 12 Feb. 2019, Japanese, Nominated symposium
  [Invited]
• 心肺運動負荷試験CPXを活用した労作時息切れの鑑別
  横田 卓
  北海道PAHレベルアップ塾, 25 Jan. 2019, Japanese, Public discourse
  [Invited]
• ICT and IoT in heart failure management and prevention
  Takashi Yokota
  The 6th SNUH-HUH-SHH Joint Symposium, 09 Nov. 2018, English, Nominated symposium
  [Invited]
• Heart failure and ICT
  Takashi Yokota
  The 9th Asian Pacific Congress of Heart Failure, 13 Oct. 2018, English, Nominated symposium
  [Invited]
• 心不全診療における包括的心臓リハビリテーション
  横田 卓
  苫小牧心不全チーム医療カンファレンス, 18 Sep. 2018, Japanese, Public discourse
  [Invited]
• セルフケアを含めた包括的心臓リハビリテーション
  横田 卓
  高齢者心不全 包括的ケア講演会, 06 Jul. 2018, Japanese, Public discourse
  [Invited]
• 心不全のお話：北海道大学における心不全治療の現状
  横田 卓
  時計台循環器ミーティング, 16 Jan. 2018, Japanese, Public discourse
  [Invited]
• 心不全治療における遠隔モニタリング
  横田 卓
  第21回日本適応医学会学術集会, 02 Dec. 2017, Japanese, Nominated symposium
  [Invited]
• 高齢心不全に対する ICTを活用した次世代型疾病管理
  横田 卓
  高齢化社会における循環器疾患の現状と展望, 29 Nov. 2017, Japanese, Keynote oral presentation
  [Invited]
• 心不全を合併した Loeys-Dietz症候群の一例
  横田 卓; 津田 正哉; 松島 将士
  第118回日本循環器学会北海道地方会, 25 Nov. 2017, Japanese, Oral presentation
• 内科・外科の垣根を越えた包括的心不全治療
  横田 卓
  心不全治療のTotal Management, 18 Oct. 2017, Japanese, Public discourse
  [Invited]
• ICTを活用した心不全の 次世代型疾病管理
  横田 卓; 筒井 裕之
  第4回日本心血管脳卒中学会学術集会, 03 Jun. 2017, Japanese, Nominated symposium
  [Invited]
• A novel self-care management tool using information and communication technology for elderly patients with heart failure
  Takashi Yokota; Miyuki Tsuchihashi-Makaya; Masanori Yoshino; Hiroyuki Tsutsui
  Japan Circulation Society (JCS) Scientific Sessions 2017, 17 Mar. 2017, English, Nominated symposium
  [Invited]
• Pioglitazone improves aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome
  Takashi Yokota; Shintaro Kinugawa; Kagami Hirabayashi; Tadashi Suga; Shingo Takada; Koichi Okita; Hiroyuki Tsutsui
  Japan Heart Failure Society Scientific Session 2016, 07 Oct. 2016, English, Oral presentation
• 高度の心機能異常を呈したダノン病の一例
  横田 卓
  北海道先天性代謝異常研究会, 27 Aug. 2016, Japanese, Oral presentation
• 生活習慣病・心血管病における 骨格筋ミトコンドリアの役割
  横田 卓
  クリニカルサイエンス談話会, 28 Apr. 2016, Japanese, Public discourse
  [Invited]
• Advanced self-care support system using information and communication technology (ICT) for patients with chronic heart failure
  Takashi Yokota; Miyuki Tsuchihashi-Makaya; Arata Fukushima; Yoko Ikeda; Takahiro Abe; Shingo Takada; Akimichi Saito; Wataru Takeuchi; Tomohiko Mizuguchi; Keiji Kobashi; Masanori Yoshino; Hiroyuki Tsutsui
  Japan Circulation Society (JCS) Scientific Sessions 2016, 20 Mar. 2016, Japanese, Nominated symposium
  [Invited]
• 患者中心の医療システムを実現するために
  Takashi Yokota
  COI 2021 Conference, 29 Jan. 2016, Japanese, Nominated symposium
  29 Jan. 2016 - 29 Jan. 2016, [Invited]
• 生活習慣病・心血管病における 骨格筋ミトコンドリアの役割～健康長寿を目指して～
  横田 卓
  函館循環器病懇談会, 20 Jan. 2016, Japanese, Public discourse
  [Invited]
• 心肺運動負荷検査 (CPX) を活用して“労作時息切れ”の原因を探索する
  横田 卓
  6th Young Diabetologist & Cardiologist Forum, 02 Jul. 2015, Japanese, Public discourse
  [Invited]
• Role of brain mitochondria in premature aging
  Takashi Yokota
  CCH Symposium (Taichung), 15 Nov. 2014, English, Nominated symposium
  [Invited]
• Gradual wake-up of mitochondria during early reperfusion: The effect of inhibition of the malate-aspartate shuttle on mitochondrial function and ROS production against myocardial ischemia-reperfusion injury
  Takashi Yokota
  11th ASMRM (Taipei), 14 Nov. 2014, English, Nominated symposium
  [Invited]
• Impaired mitochondrial oxidative phosphorylation and fatty acid oxidation with enhanced mitochondrial oxidative stress in spontaneously-occurring feline hypertrophic cardiomyopathy
  Takashi Yokota; Liselotte B. Christiansen; Flemming Dela
  Japan Heart Failure Society Scientific Session 2014, 10 Oct. 2014, English, Oral presentation
• 心臓リハビリテーションのガイドライン
  横田 卓
  第4回 北大病院循環器内科生涯教育講座, 25 Sep. 2014, Japanese, Public discourse
  [Invited]
• Myocardial mitochondrial respiration in human heart failure
  Flemming Dela; Nis Stride; Liselotte B. Christiansen; Takashi Yokota
  The Federation of European Physiological Societies (FEPS) (Budapest, Hungary), 28 Aug. 2014, English, Invited oral presentation
  [Invited]
• Role of brain mitochondria in premature aging
  Takashi Yokota
  BIT's 4th Annual World Congress of Molecular & Cell Biology (CMCB-2014) (Dalian, China), 27 Apr. 2014, English, Oral presentation
  [Invited]
• Role of mitochondria in ischaemia-reperfusion injury in cardiac muscle
  Takashi Yokota
  Mitochondrial Physiology 2013 (Copenhagen, Denmark), 30 Aug. 2013, English, Nominated symposium
  [Invited]
• Brain mitochondrial dysfunction in a mouse-model of premature aging
  Takashi Yokota
  Mitochondrial Physiology 2013 (Copenhagen, Denmark), 28 Aug. 2013, English, Nominated symposium
  [Invited]
• Inhibition of the malate-aspartate shuttle during early reperfusion preserves mitochondrial function and attenuates reactive oxygen species production in ischemia/reperfusion injured heart
  Takashi Yokota
  3rd Targeting Mitochondria (Berlin, Germany), 09 Nov. 2012, English, Oral presentation
• Brain Mitochondrial Dysfunction in Premature Aging Disorder
  Takashi Yokota
  CEHA-SAB Meeting (Copenhagen, Denmark), 28 Sep. 2012, English, Nominated symposium
  [Invited]
• The Effects of Malate-Aspartate Shuttle Inhibition on Mitochondrial Respiration and Oxidative Stress in Ischemia/Reperfusion Injured Heart
  Takashi Yokota
  CEHA-SAB Meeting (Copenhagen, Denmark), 28 Sep. 2012, English, Nominated symposium
  [Invited]
• Enhanced systemic oxydative stress is associated with impaired fatty acid metabolism in skeletal muscle in patients with metabolic syndrome
  Takashi Yokota; Shintaro Kinugawa; Kagami Hirabayashi; Tadashi Suga; Shingo Takada; Koichi Okita; Flemming Dela; Hiroyuki Tsutsui
  MiP Conference 2011 (Bordeaux, France), 06 Sep. 2011, English, Oral presentation
• インスリン抵抗性と酸化ストレス～骨格筋ミトコンドリア～
  横田 卓
  Young Diabetologist and Cardiologist Forum 2011, 03 Feb. 2011, Japanese, Public discourse
  [Invited]
• Pioglitazone increases the aerobic capacity with improved skeletal muscle energetics in patients with insulin resistance
  Takashi Yokota; Shintaro Kinugawa; Kagami Hirabayashi; Tadashi Suga; Shingo Takada; Masashige Takahashi; Taisuke Ono; Sobilin A. Mochamad; Koichi Okita; Hiroyuki Tsutsui
  European Association for the Study of Diabetes (EASD) Annual Meeting 2010 (Stockholm, Sweden), 21 Sep. 2010, English, Oral presentation
• Pioglitazone improves aerobic capacity and skeletal muscle high-energy phosphate metabolism in patients with metabolic syndrome
  Yokota T; Kinugawa S; Hirabayashi K; Suga T; Matsushima S; Sobirin AM; Ono T; Morita N; Takada S; Omokawa M; Okita K; Tsutsui H
  American Heart Association (AHA) Scientific Sessions 2009 (Orlando), 18 Nov. 2009, English, Oral presentation
• 致死性不整脈を合併した冠攣縮性狭心症
  横田 卓; 榊原 守; 山田 史郎; 正木 芳宏; 筒井 裕之
  日本心血管インターベンション学会 (CVIT) 第29回北海道地方会, 12 Sep. 2009, Japanese, Oral presentation
• Lowered aerobic exercise capacity was associated with impaired skeletal muscle metabolism in patients with metabolic syndrome
  Japan Circulation Society (JCS) Scientific Sessions 2009, 22 Mar. 2009, Japanese, Oral presentation
• Impaired skeletal muscle energy metabolism limits systemic aerobic exercise capacity in patients with metabolic syndrome
  Yokota T; Kinugawa S; Hirabayashi K; Suga T; Morita N; Inoue N; Ohta Y; Matsushima S; Sobirin AM; Hamaguchi S; Ono T; Horiuchi M; Okita K; Tsutsui H
  American Heart Association (AHA) Scientific Sessions 2008 (New Orleans), 10 Nov. 2008, English, Oral presentation
• メタボリック症候群では、骨格筋エネルギー代謝異常が有酸素運動能を低下させる
  横田 卓; 絹川 真太郎; 平林 鑑; 菅 唯志; 濱口 早苗; 小野 太祐; ソビリン アリ; 高田 真吾; 面川 雅司; 沖田 孝一; 筒井 裕之
  第58回循環器負荷研究会, 02 Aug. 2008, Japanese, Oral presentation
• Lowered aerobic exercise capacity was associated with impaired skeletal muscle metabolism in patients with metabolic syndrome
  Yokota T; Kinugawa S; Hirabayashi K; Suga T; Morita N; Inoue N; Ohta Y; Matsushima S; Sobirin AM; Hamaguchi S; Ono T; Horiuchi M; Okita K; Tsutsui H
  European College of Sport Science (ECSS) 2008 (Estoril, Portugal), 10 Jul. 2008, English, Oral presentation
• Oxidative stress impairs mitochondrial respiration in skeletal muscle and limits exercise capacity in diabetic mice
  Yokota T; Kinugawa S; Matsushima S; Inoue N; Ohta Y; Hirabayashi K; Hamaguchi S; Ono T; Okita K; Tsutsui H
  Japan Circulation Society (JCS) Scientific Sessions 2008, 30 Mar. 2008, Japanese, Oral presentation
• 糖尿病モデルマウスにおいてNAD(P)H oxidase 由来の骨格筋酸化ストレス (O2-)が 運動能力を制限する
  横田 卓; 絹川 真太郎; 松島 将士; 井上 直樹; 大田 幸博; 濱口 早苗; ソビリン モハマド アリ; 小野 太祐; 平林 鑑; 沖田 孝一; 筒井 裕之
  第57回循環器負荷研究会, Aug. 2007, Japanese, Oral presentation
• Superoxide anion (O2-) derived from NADPH oxidase impairs mitochondrial oxidative respiration in skeletal muscle and limits exercise capacity in diabetic mice
  Takashi Yokota; Shintaro Kinugawa; Syouji Matsushima; Naoki Inoue; Yukihiro Ohta; Sanae Hamaguchi; Kouichi Okita; Hiroyuki Tsutsui
  The American College of Sports Medicine (ACSM) Annual Meeting 2007 (New Orleans), 01 Jun. 2007, English, Oral presentation
  30 May 2007 - 02 Jun. 2007
• Reactive oxygen species derived from NAD(P)H oxidase cause the limitation of exercise capacity in diabetic mice
  Takashi Yokota; Shintaro Kinugawa; Syouji Matsushima; Naoki Inoue; Yukihiro Ohta; Sanae Hamaguchi; Kouichi Okita; Hiroyuki Tsutsui
  Japan Circulation Society (JCS) Scientific Sessions 2007, 16 Mar. 2007, Japanese, Oral presentation
• インスリン抵抗性が運動能力・骨格筋機能に及ぼす影響
  横田 卓; 絹川 真太郎; 松島 将士; 井上 直樹; 大田 幸博; 濱口 早苗; 沖田 孝一; 筒井 裕之
  第56回循環器負荷研究会, 05 Aug. 2006, Japanese, Oral presentation
• 左室拡張機能評価が無症候性心筋虚血診断 の端緒となった発作性心房細動の1例
  横田 卓; 山田 聡; 小松 博史; 小室 薫; 加賀 早苗; 横式 尚司; 浦沢 一史; 佐久間 一郎; 北畠 顕
  第231回日本内科学会北海道地方会, 05 Jun. 2004, Japanese, Oral presentation

• ゲノム情報科学特論, 2024年, 修士課程, 情報科学院
• ゲノム情報科学特論, 2024年, 博士後期課程, 情報科学研究科
• ゲノム情報科学特論, 2024年, 博士後期課程, 情報科学院

• ひと・AI/DX・しくみの三位一体的整備による次世代AI活用・データ駆動・情報循環型医学研究の戦略的推進 (PRISM-HU)
  医学系研究支援プログラム
  Oct. 2025 - Mar. 2028
  日本医療研究開発機構 (AMED), 北海道大学
• 冬眠原理の追求とその社会展開に向けた分野横断型基礎研究
  J-PEAKs アクセラレーションステージ
  Apr. 2025 - Mar. 2028
  山口 良文; 岡松 優子; 曽根 正光; 山内 彩加林; 下鶴 倫人; 加藤 美羅; 山仲 勇二郎; 新宮 康栄; 横田 卓; 高氏 修平
  国立大学法人北海道大学, 北海道大学, Coinvestigator
• 生活習慣病・認知症の遺伝学的リスク評価が被検者のライフスタイルに及ぼす影響
  科学研究費助成事業
  Apr. 2025 - Mar. 2028
  横田 卓; 畑中 豊
  日本学術振興会, 基盤研究(C), 北海道大学, Principal investigator, 25K14955
• Real World Evidence創出のための取り組み (臨中ネット)
  医療技術実用化総合促進事業
  Apr. 2019 - Mar. 2028
  日本医療研究開発機構 (AMED), 北海道大学病院
• 治験・臨床試験におけるAI利活用の推進に係る取組み
  医療技術実用化総合促進事業
  Feb. 2026 - Mar. 2027
  日本医療研究開発機構 (AMED), 北海道大学病院
• 北の社会イノベーション
  Jan. 2025 - Mar. 2027
  横田 卓
  日立北大ラボ, 北海道大学, Coinvestigator
• 分散型臨床試験 (DCT) の取り組み
  医療技術実用化総合促進事業
  Apr. 2022 - Mar. 2027
  日本医療研究開発機構 (AMED), 北海道大学病院
• 日本ハムファイターズ選手を対象としたOura Ringを用いた睡眠などのデータ収集・評価および睡眠改善を目指した研究
  Jun. 2022 - Mar. 2026
  山仲 勇二郎; 横田 卓
  株式会社Ambi・北海道日本ハムファイターズ, Coinvestigator
• 心房細動の病態進行における心臓周囲脂肪ミトコンドリア機能の役割
  科学研究費助成事業
  Apr. 2022 - Mar. 2025
  渡邉 昌也; 畑中 豊; 新宮 康栄; 横田 卓
  日本学術振興会, 基盤研究(C), 北海道大学, Coinvestigator, 22K08197
• 末梢血単核球ミトコンドリア機能を筋ジストロフィーの重症度評価・治療に応用する。
  科学研究費助成事業
  Apr. 2021 - Mar. 2025
  山澤 弘州; 武田 充人; 横田 卓; 矢部 一郎
  筋ジストロフィーはいまだ根本的な治療法が見つかっていない難治性の遺伝性疾患である。初発の症状は骨格筋障害による運動機能低下であるが、病状の進行に伴い多臓器障害および全身の代謝異常を来たし、終末期には生活の質 (QOL) の著しい低下により寝たきり状態となり、多くは心不全または致死性不整脈により死亡する。この筋ジストロフィーの臨床像は骨格筋・心筋障害を主症状とするミトコンドリア病と多くの点で類似している。これまでにも筋ジストロフィーの発症・進展にミトコンドリア機能障害が関与している可能性が示唆されていたが、ヒトの骨格筋や心筋から組織を採取しミトコンドリア機能を直接
  測定することは侵襲性の面で困難であり、十分に検証されてこなかった。
  そこで本研究の最終目的は侵襲の少ない末梢血単核球(PBMC)を用い、『筋ジストロフィーの進展にはPBMCミトコンドリア機能異常が関わっており、骨格筋障害のみならず心筋障害などの多臓器不全に関与する』という仮説を検証することにある。
  仮説が正しいなら筋ジストロフィーにおいて実際PBMCミトコンドリア機能異常がある事を証明することがまず第一歩になる。下記の進捗に示す通り対象者のリクルートは概ね順調に進んでおり、結果の詳細はここでは控えさせて頂きたいが、測定も順調に進んでいる。
  更に骨格筋機能や画像による心機能、心筋障害評価結果との関連性の検討を現在進行形で進めている。統計学的な解析結果はここでは控えさせて頂きたい。
  日本学術振興会, 基盤研究(C), 北海道大学, Coinvestigator, 21K08071
• The study for prevention of cardiovascular disease by machine learning model using personal health records
  Grants-in-Aid for Scientific Research
  Apr. 2021 - Mar. 2025
  Takashi Yokota; Shinji Nakaoka; Kiminori Nakamura
  わが国は超高齢社会を迎え、心血管病の患者数は増加の一途を辿っており、早急に患者本人が主体的にセルフモニタリングを行い疾病予防に取り組む「患者中心の医療 (patient-centered care)」 を実現する必要に迫られている。心血管病の予防・治療の基本は食事・運動をはじめとする生活習慣の是正であるが、在宅で取得可能なパーソナル・ヘルス・レコード (PHR) の活用が必要不可欠である。さらにCOVID-19感染拡大をきっかけにオンライン診療が広く推奨されるようになり、とりわけ情報通信技術 (ICT) を活用したPHRのニーズが高まっている。そこで我々は、在宅で取得するPHRを活用し適切なセルフケアの実践を促すスマートフォン対応セルフケアサポートアプリを開発した。本研究の目的は、このアプリで収集する血圧・体重・体脂肪率・体温・酸素飽和度・塩分摂取量・身体活動量・睡眠時間などのバイタルサインや食事・運動内容、さらには便を用いた腸内フローラ解析データなどの多様なPHRを活用し、機械学習モデルを用いて、心血管病の重症化予測を行うとともに重症化予防のための個々に最適な食事・運動療法を提案することである。
  臨床試験『スマートフォンアプリを活用した統合型高血圧セルフケアサポートシステムの有効性の検証 (AppCare-HT Study)』については、全症例数 (360名) のフォローアップが完了し、論文化へ向けて解析を進めている。また、心不全患者を対象にした臨床試験についても研究実施中で、順次データ解析を進めている。
  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 21K08120
• Development of early detection method for adriamycin-induced cardiomyopathy based on the immunosenescence
  Grants-in-Aid for Scientific Research
  Apr. 2021 - Mar. 2024
  石森 直樹; 横田 卓; 加畑 馨
  近年わが国では急速な高齢化が進行してがん患者数は増加し、国民の２人に１人は生涯がんに罹患すると言われている。がんの早期発見や治療法の進歩により、がん患者の生命予後は著しく改善してきたが、再発がん患者では「がん死」に次いで死因第２位に「心血管病」が挙がっており、がん診療での心血管病の制御はきわめて重要な課題となっている。
  アドリアマイシンをはじめとするアントラサイクリン系抗がん剤は、分子標的薬が登場した現代においてもリンパ腫、乳がんおよび肉腫などに対する標準的化学療法薬として重要な位置づけにある。しかし、累積使用量（アドリアマイシン換算）400mg/m2で約5％、700mg/m2では約25％と用量依存的に心筋障害を合併し、時に難治性心不全をきたして死に至る。疫学研究によって累積使用量のほか、年齢や放射線治療歴など心筋障害合併リスク因子が明らかにされているが、化学療法から年余を経て突然心不全を発症し、薬剤性心筋症と診断される例も少なくなく、細心の注意が必要である。
  近年、加齢関連疾患の病態形成においていわゆる老化関連T細胞が出現する「免疫老化」の寄与が注目されている。我々はアドリアマイシン心筋症の発症・進展において「免疫老化」を基盤として慢性炎症が遷延し、心筋症発症に寄与するとの仮説を立てた。本研究の遂行によって、アドリアマイシン心筋症発症リスクのより正確な予測が可能となるばかりでなく、慢性炎症の制御という新たなコンセプトに基づくアドリアマイシン心筋症の予防・治療法の開発に貢献することが期待して本研究を立案した。
  現在、標準的化学療法薬としてアドリアマイシンを用いたレジメで治療された悪性リンパ腫患者の治療フローを確認しながら、アドリアマイシン心筋症に関するレジストリ構築中である。
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Coinvestigator, 21K08046
• マイオカインによる老化進展制御機構の解明
  科学研究費助成事業
  Apr. 2021 - Mar. 2024
  絹川 真太郎; 佐邊 壽孝; 高田 真吾; 松島 将士; 横田 卓
  日本学術振興会, 基盤研究(B), 九州大学, Coinvestigator, 21H03360
• Role of alpha-defensins derived from the small intestine and gut microbiota in heart failure
  Grants-in-Aid for Scientific Research
  Apr. 2018 - Mar. 2024
  Takashi Yokota; Toshihisa Anzai; Tokiyoshi Ayabe; Shintaro Kinugawa; Arata Fukushima
  心不全の発症・進展において全身の慢性炎症が重要な役割を果たしていることは広く知られており、全身の免疫に関わる腸内フローラの役割に関心が集まっている。本研究では、この腸内フローラを制御する抗菌ペプチドである小腸Paneth細胞由来αディフェンシン (HD5; human defensin-5) の役割に着目し、『心不全患者では小腸Paneth細胞由来αディフェンシンの産生量が低下しており、腸内環境の破綻”dysbiosis”が全身炎症を惹起し、心不全の進展に寄与する』という仮説を検証することを目的とし、基礎・臨床研究の両面から、心腸連関として心不全が腸内環境に及ぼす影響を評価することとした。
  基礎研究については、左冠動脈結紮による心筋梗塞モデルマウス (MIマウス) を用いて評価を行ったところ、shamマウス (対照群) と比較して、心筋梗塞発症
  早期よりPaneth細胞由来のαディフェンシン産生量が減少し、小腸陰窩の萎縮ならびにPaneth細胞数の減少を認めた。一方、心筋梗塞発症後28日目には心不全を発症しており、αディフェンシン産生量の減少のみならず、腸内フローラのα多様性およびβ多様性の低下を認め、dysbiosisが生じていた。
  臨床研究「心不全における腸管上皮細胞由来αディフェンシンの役割 (UMIN: 000032796)」については、これまでに計49例 (心不全患者39例・健常者10例) が参加した。今後さらに症例数を増やしていくとともに、今後小腸Paneth細胞由来のαディフェンシン産生量および腸内フローラの多様性と心不全重症度との関連を評価する予定である。
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 18K08022
• Impact of myocardial fibrosis on exercise capacity in heart failure with preserved ejection fraction
  Grants-in-Aid for Scientific Research
  01 Apr. 2018 - 31 Mar. 2022
  Iwano Hiroyuki
  Impaired exercise tolerance is a major symptom of heart failure, and heart failure with preserved left ventricular ejection fraction (HFpEF) has a phenotype with no apparent organic abnormalities in the left ventricle. Because the determinants of tolerance in this etiology are not clear, the mechanism of decreased exercise tolerance in this pathological condition was investigated using exercise echocardiography and cardiac MRI.
  Cardiopulmonary exercise testing, exercise echocardiography, and contrasted-enhanced cardiac MRI were performed in 49 HFpEF patients without left ventricular hypertrophy, and the determinants of exercise tolerance were examined. As a result, exercise-induced pulmonary hypertension and impaired right ventricular-pulmonary artery coupling, rather than LV diastolic dysfunction, were found to be associated with exercise tolerance.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 18K07622
• Center of Innovation Program from the Japan Science and Technology Agency (JPMJCE1301)
  Center of Innovation Program
  Apr. 2015 - Mar. 2022
  Japan Science and Technology Agency, Hokkaido University, Coinvestigator
• Study on the mechanism of regulation of mitochondrial function by brain-derived neurotrophic factor
  Grants-in-Aid for Scientific Research
  01 Apr. 2018 - 31 Mar. 2021
  Kinugawa Shintaro
  We clarified that brain-derived neurotrophic factor (BDNF) is a myokine secreted from skeletal muscle cells, and found that it is present in mitochondria in skeletal muscle cells. We found that BDNF plays an important role in regulating the amount and function of skeletal muscle mitochondria, especially in fatty acid oxidation. Furthermore, these effects of BDNF were mediated by AMPKα and PGC-1α signals. Administration of human recombinant BDNF to post-myocardial infarction heart failure model mice increased skeletal muscle BDNF, improved AMPKα-PGC-1α signal, and improved endurance exercise capacity. The therapeutic effect of BDNF was equivalent to that of exercise therapy, and was mediated by the same signal.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), 18H03187
• The role of protein lysine-acetlation in congenital heart disease
  Grants-in-Aid for Scientific Research
  01 Apr. 2017 - 31 Mar. 2020
  FUKUSHIMA ARATA
  We investigated the maturational changes in cardiac energy metabolism in congenital heart disease (CHD) with heart failure. The CHD model was created using newborn rabbits subjected to an aortocaval shunt. Decreased cardiac fatty acid oxidation along with decline in energy production occurred in CHD group compared to sham group. In addition, reduced acetylation, an important post-translational modification of proteins, of fatty acid β-oxidation enzymes, LCAD and β-HAD, was observed in CHD group, associated with reduced enzymatic activities and fatty acid oxidation rates. Of note, the expression of the mitochondrial acetyltransferase, GCN5L1, was reduced in CHD group, and silencing GCN5L1 mRNA in cultured cardiomyocytes (H9c2 cells) significantly reduced acetylation and activity of LCAD and β-HAD, leading to an overt cardiac hypertrophy. A similar phenomenon was also proved in studies using myocardial specimens of patients with congenital heart disease.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 17K10137
• Study for prevention of hypertensive disease progression using self-care
  平成30年度 IoT等活用行動変容研究事業研究事業
  Aug. 2018 - Mar. 2020
  Japan Agency for Medical Research and Development, Hokkaido University, Coinvestigator
• Effects of skeletal muscle ischemic preconditioning for fatigability and damage protection
  Grants-in-Aid for Scientific Research
  01 Apr. 2015 - 31 Mar. 2018
  OKITA KOICHI
  First, we examined the effective repetition numbers (from zero to four) of direct and remote ischemic preconditioning in lower leg on exercise performance and fatigability. Contrary to previous reports, the results showed that any repetition of IPC did not affect the maximum strength and fatigability in knee extension. We reported those preliminary results at annual meeting of the Japanese Society of Physical Fitness and Sports Medicine (2016, 2017). Concerning those negative results, we examined effects of IPC in a practical exercise of repeated-jump and combined IPC with dietary nitrate (donor of nitric oxide). However, we could not demonstrate significant effects of IPC on exercise performance and muscle damage even with dietary nitrate (annual meeting of Japanese Association of Exercise Therapy and Prevention, JACR 2017). We are preparing to present the summaries of those results at annual scientific meetings and to submit them to international journals.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokusho University, 15K01625
• Role of epicardial adipose tissue mitochondria in cardiovascular disease
  Grants-in-Aid for Scientific Research
  Apr. 2015 - Mar. 2018
  Takashi Yokota; Shintaro Kinugawa; Hiroyuki Tsutsui; Shouji Matsushima
  Epicardial adipose tissue (EAT), a source of adipokines, is metabolically active. However, the role of EAT mitochondria in coronary artery disease (CAD) has not been established. We investigated the association between mitochondrial function in the EAT and coronary atherosclerosis. EAT samples were obtained from 25 patients who underwent elective cardiac surgery. The patients were divided into CAD (n=14) and non-CAD (n=11) groups. Mitochondrial oxidative phosphorylation (OXPHOS) capacity in the EAT was significantly lowered in CAD patients. The mitochondrial OXPHOS capacity in the EAT was positively correlated to protein content of adiponectin in the EAT, and inversely correlated to severity of coronary artery stenosis. Collectively, the findings of the present study support the hypothesis that impaired mitochondrial respiratory capacity in the EAT plays a crucial role in the progression of coronary atherosclerosis, at least in part via reduced adiponectin synthesis in the EAT.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 15K09115
• The role of mitoNEET on the regulation of mitochondrial function in skeletal muscle failure
  Grants-in-Aid for Scientific Research
  01 Apr. 2014 - 31 Mar. 2017
  Kinugawa Shintaro; FURIHATA Takaaki; TAKADA Shingo
  In various chronic disease model mice, exercise capacity was reduced, skeletal muscle abnormalities such as mitochondrial dysfunction in the skeletal muscle and fiber type switch occurred, iron content within mitochondria was increased, and oxidative stress was enhanced. In mice deleted mitoNEET, we newly created, iron content within mitochondria was increased, oxidative stress was enhanced, and mitochondrial morphology and function was impaired, which resulted in the reduced exercise capacity. There were no differences in the known protein associated with iron homeostasis in mitochondria. In the analysis by protein interaction, we found that mitoNEET combined with cytosolic protein X associated with iron homeostasis and mitochondrial inner membrane protein Y associated with transportation of some substances into mitochondria.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 26350879
• Study for Development and Verification of Telemedicine for Stroke and Cardiovascular Disease
  Practical Research Project for Life-Style Related Diseases Including Cardiovascular Diseases and Diabetes Mellitus
  Sep. 2015 - Mar. 2017
  Japan Agency for Medical Research and Development, Hokkaido University, Coinvestigator
• Resistance training with blood flow restriction: from basic physiological study to creative clinical application
  Grants-in-Aid for Scientific Research
  2011 - 2013
  OKITA KOICHI; KINUGAWA Shintaro; YOKOTA Takashi; HORIUCHI Masahiro; MORITA Noriteru
  We demonstrated that enhanced metabolic stress in exercising muscle is a key mechanism for favorable effects by resistance training and the elevated metabolic stress appears to be a crucial factor in obtaining successful results from resistance training (J Appl Physiol 2012). Based on these findings, we proposed the guidelines of resistance exercise with blood flow restriction for healthy subjects and diseased subjects such as diabetes and heart failure by considering individual characteristics, training status, disease status, age, and gender difference (Med Sci Sports Exerc 2012, Eur J Appl Physiol 2012, Jpn Coll Angiol 2012, Circ J 2013). Moreover, we applied this procedure to different types of athletes, sprinters and endurance runners, and also young athletes (Int J Vasc Med 2012, J Nov Physiother 2013).
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokusho University, 23500784

• Method for evaluating pathology of cardiac failure
  Patent right, Shingo Takada; Satoshi Maekawa; Takashi Yokota; Ryosuke Shirakawa; Hisataka Sabe, Hokkaido University
  特願2020-548000, 28 Jun. 2019
  WO2020059242, 26 Mar. 2020
  特許7430916
  14 Feb. 2024

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  楽しく知ろう！ハートケア最前線 心不全撲滅宣言 2023 in SAPPORO
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