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Exercise training reveals micro-RNAs associated with improved cardiac function and electrophysiology in rats with heart failure after myocardial infarction.
Stølen, Tomas O; Høydal, Morten A; Ahmed, Muhammad Shakil; Jørgensen, Kari; Garten, Karin; Hortigon-Vinagre, Maria P; Zamora, Victor; Scrimgeour, Nathan R; Berre, Anne Marie Ormbostad; Nes, Bjarne M; Skogvoll, Eirik; Johnsen, Anne Berit; Moreira, Jose B N; McMullen, Julie R; Attramadal, Håvard; Smith, Godfrey L; Ellingsen, Øyvind; Wisløff, Ulrik.
Afiliación
  • Stølen TO; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway; Department of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Cardiothoracic Surgery, St. Olavs Hospital,
  • Høydal MA; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway; Department of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Cardiothoracic Surgery, St. Olavs Hospital,
  • Ahmed MS; Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Jørgensen K; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • Garten K; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • Hortigon-Vinagre MP; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Science, University of Glasgow 126 University Place, Glasgow G12 8TA, United Kingdom.
  • Zamora V; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Science, University of Glasgow 126 University Place, Glasgow G12 8TA, United Kingdom.
  • Scrimgeour NR; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • Berre AMO; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • Nes BM; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway; Department of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
  • Skogvoll E; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway; Department of Anesthesia and Intensive Care Medicine, St. Olav University Hospital, Trondheim, Norway.
  • Johnsen AB; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • Moreira JBN; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • McMullen JR; Cardiac Hypertrophy Laboratory, Baker Heart & Diabetes Institute, 75 Commercial Road, Melbourne, VIC, Australia.
  • Attramadal H; Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Smith GL; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Science, University of Glasgow 126 University Place, Glasgow G12
  • Ellingsen Ø; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway; Department of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
  • Wisløff U; Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway; School of Human Movement & Nutrition Sciences, University of Queensland, Australia.
J Mol Cell Cardiol ; 148: 106-119, 2020 11.
Article en En | MEDLINE | ID: mdl-32918915
AIMS: Endurance training improves aerobic fitness and cardiac function in individuals with heart failure. However, the underlying mechanisms are not well characterized. Exercise training could therefore act as a tool to discover novel targets for heart failure treatment. We aimed to associate changes in Ca2+ handling and electrophysiology with micro-RNA (miRNA) profile in exercise trained heart failure rats to establish which miRNAs induce heart failure-like effects in Ca2+ handling and electrophysiology. METHODS AND RESULTS: Post-myocardial infarction (MI) heart failure was induced in Sprague Dawley rats. Rats with MI were randomized to sedentary control (sed), moderate (mod)- or high-intensity (high) endurance training for 8 weeks. Exercise training improved cardiac function, Ca2+ handling and electrophysiology including reduced susceptibility to arrhythmia in an exercise intensity-dependent manner where high intensity gave a larger effect. Fifty-five miRNAs were significantly regulated (up or down) in MI-sed, of which 18 and 3 were changed towards Sham-sed in MI-high and MI-mod, respectively. Thereafter we experimentally altered expression of these "exercise-miRNAs" individually in human induced pluripotent stem cell-derived cardiomyocytes (hIPSC-CM) in the same direction as they were changed in MI. Of the "exercise-miRNAs", miR-214-3p prolonged AP duration, whereas miR-140 and miR-208a shortened AP duration. miR-497-5p prolonged Ca2+ release whereas miR-214-3p and miR-31a-5p prolonged Ca2+ decay. CONCLUSION: Using exercise training as a tool, we discovered that miR-214-3p, miR-497-5p, miR-31a-5p contribute to heart-failure like behaviour in Ca2+ handling and electrophysiology and could be potential treatment targets.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Condicionamiento Físico Animal / MicroARNs / Fenómenos Electrofisiológicos / Insuficiencia Cardíaca / Infarto del Miocardio Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: J Mol Cell Cardiol Año: 2020 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Condicionamiento Físico Animal / MicroARNs / Fenómenos Electrofisiológicos / Insuficiencia Cardíaca / Infarto del Miocardio Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: J Mol Cell Cardiol Año: 2020 Tipo del documento: Article