Combinatorial microRNAs suppress hypoxia-induced cardiomyocytes apoptosis.

BACKGROUND/AIMS: Our previous in silico analysis revealed potential synergy in the activities of micro(mi)RNAs in myocardial infarction. The present study investigated whether miR-1 and -21 act synergistically to protect against cardiomyocytes apoptosis.

METHODS

Cell survival was analyzed with cell viability assay; apoptosis was detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling, and the caspase-3 activity assay; and protein expression level was determined by western blotting.

RESULTS

MiR-1:miR-21 and several other miRNA pairs were evaluated for their potentially synergistic effects against myocardial hypoxia in neonatal rat ventricular cardiomyocytes. Lower combination indices suggested that miRNA pairs acted synergistically to inhibit apoptosis; miR-1 and -21 jointly blocked hypoxia-induced cardiomyocytes apoptosis. Moreover, combined application of miR-1 and -21 activated Akt and blocked hypoxia-induced upregulation of p53 in these cells.

CONCLUSION

MiR-1 and -21 exert synergistic effects against hypoxia-induced cardiomyocytes apoptosis. These results provide a basis for the development of combined miRNA-based therapeutics to treat cardiovascular diseases.