Furthermore, our results showed that the concentrations of plasma miR-499-5p could be correlated with myocardial infarction (MI) and heart failure (HF) patients in comparison with control subjects and polymorphism rs3746444 in miR-499 could influence its abundance in plasma.
Increased miRNA levels were strongly associated with increased risk of mortality or heart failure within 30 days for miR-208b (OR 1.79, 95% CI = 1.38-2.23, p = 1 × 10(-5)) and miR-499-5p (OR 1.70, 95% CI = 1.31-2.20, p = 5 × 10(-5)) but the association was lost when adjusting for Troponin T. During surgery miR-208b and miR-499-5p was released in the coronary sinus after cardioplegia-reperfusion to markedly higher levels than in a peripheral vein.
Forced cardiomyocyte expression of miR-499 at levels comparable to human cardiomyopathy induced progressive murine heart failure and exacerbated cardiac remodeling after pressure overloading.
Both wild-type and mutant miR-499 induced heart failure in mice, but miR-499 c17 misdirected recruitment of a subset of miR-499 target mRNAs to cardiomyocyte RNA-induced silencing complexes, altering steady-state cardiac mRNA and protein make-up and favorably impacting cardiac function.
The recognition that miR-499 promotes the differentiation of hCSCs into mechanically integrated cardiomyocytes has important clinical implications for the treatment of human heart failure.