Abstract
Background: Exercise training is recommended as a useful intervention in cardiac rehabilitation for patients with chronic heart failure. There has been emerging evidence indicating that circulating microRNA (miRNA, miR) could mediate the beneficial effects of exercise in both healthy persons and patients with cardiovascular diseases. The current study was aimed to investigate the regulation of circulating miRNAs in response to an acute exhaustive exercise in patients with chronic heart failure (CHF). Methods: Twenty-eight CHF patients (mean age=59.07±1.79 years, 14 in NYHA Class II and 14 in NYHA Class III) performed a symptom-limited incremental cardiopulmonary exercise test on a bicycle ergometer according to a standardized exercise protocol of revised Ramp10 programs (acute exercise). Serum samples were collected before and immediately after exercise session. The cardiac or muscle specific/enriched miRNAs including miR-1, miR-133a, miR-133b, miR-499, miR-208a, miR-208b, miR-378, miR-486, and miR-940 were determined. In addition, other miRNAs involved in angiogenesis (miR-20a, miR-328, miR-126, miR-221), inflammation (miR-21, miR-146a, miR-155), and ischemia adaptation (miR-210, miR-21, miR-146a) were also investigated. Moreover, inflammatory and muscle damage markers including creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), troponin T (Tn-T), N-terminal pro-brain natriuretic peptide (NT-ProBNP) and high sensitive C reactive protein (hs-CRP) were determined by enzyme linked immunosorbent assays (ELISA). Results: Serum miR-21, -378, and -940 were found to be significantly increased in response to acute exercise in CHF patients. In addition, no robust correlation was identified between changes of these miRNAs and muscle damage or inflammation, indicating a distinct adaptation by miRNAs. However, a linear correlation between the change of miR-21 and VO2max was observed (R=0.42, P=0.03). Conclusion: Our data suggest that circulating miR-21, miR-378, and miR-940 might be potential biomarkers for the improvement of exercise capacity in patients with chronic heart failure.
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