4.5 Article

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

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

  1. Kristian Gerhard Jebsen Foundation
  2. Liaison Committee for Education, Research and Innovation in Central Norway
  3. Norwegian Health Association
  4. Unikard
  5. Norwegian Research Council
  6. Fundacion Alfonso Martin Escudero, Spain

向作者/读者索取更多资源

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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