期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 148, 期 -, 页码 106-119出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2020.08.015
关键词
Excitation-contraction coupling; Action potential; Exercise training; Heart failure; micro RNA; Ventricular arrhythmia
资金
- Kristian Gerhard Jebsen Foundation
- Liaison Committee for Education, Research and Innovation in Central Norway
- Norwegian Health Association
- Unikard
- Norwegian Research Council
- Fundacion Alfonso Martin Escudero, Spain
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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