Exercise training reveals micro-RNAs associated with improved cardiac function and electrophysiology in rats with heart failure after myocardial infarction.

Sep 14, 2020

Contributor: Tomas O Stølen,Morten A Høydal,Muhammad Shakil Ahmed,Kari Jørgensen,Karin Garten,Maria P Hortigon-Vinagre,Victor Zamora,Nathan R Scrimgeour,Anne Marie Ormbostad Berre,Bjarne M Nes,Eirik Skogvoll,Jose Bianco Moreira,Julie R McMullen,Håvard Attramadal,Godfrey L Smith,Øyvind Ellingsen,Ulrik Wisløff

Exercise training reveals micro-RNAs associated with improved cardiac function and electrophysiology in rats with heart failure after myocardial infarction.

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 Ca handling and electrophysiology with micro-RNA (miRNA) profile in exercise trained heart failure rats to establish which miRNAs induce heart failure-like effects in Ca handling and electrophysiology.
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, Ca 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 Ca release whereas miR-214-3p and miR-31a-5p prolonged Ca decay.
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 Ca handling and electrophysiology and could be potential treatment targets.

Copyright © 2020. Published by Elsevier Ltd.

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About The Expert

Tomas O Stølen

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, Trondheim University Hospital, Trondheim, Norway. Electronic address: tomas.stolen@ntnu.no.

Morten A Høydal

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, Trondheim University Hospital, Trondheim, Norway.

Muhammad Shakil Ahmed

Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Kari Jørgensen

Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.

Karin Garten

Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.

Maria P Hortigon-Vinagre

Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Science, University of Glasgow 126 University Place, Glasgow G12 8TA, United Kingdom.

Victor Zamora

Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Science, University of Glasgow 126 University Place, Glasgow G12 8TA, United Kingdom.

Nathan R Scrimgeour

Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.

Anne Marie Ormbostad Berre

Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.

Bjarne M Nes

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.

Eirik Skogvoll

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.

Jose Bianco Moreira

Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway.

Julie R McMullen

Cardiac Hypertrophy Laboratory, Baker Heart & Diabetes Institute, 75 Commercial Road, Melbourne, VIC, Australia.

Håvard Attramadal

Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Godfrey L Smith

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 8TA, United Kingdom.

Øyvind Ellingsen

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.

Ulrik Wisløff

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.

References

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