Overexpression of miR-431 inhibits cardiomyocyte apoptosis following myocardial infarction via targeting HIPK3.

OBJECTIVE Acute myocardial infarction (AMI) is a common acute cardiovascular crisis. Although the diagnosis and treatment of AMI are constantly improving, the mortality of AMI is still very high, and its pathogenesis is still unclear. This article focuses on the role of microRNA-431 (miR-431) in regulating myocardial apoptosis after myocardial infarction (MI) and its potential molecular mechanism. MATERIALS AND METHODS We constructed cell models and animal models of MI. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was used to detect miR-431 expression in myocardium after MI. Western blot, cell counting kit-8 (CCK-8) assay, flow cytometry and terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) staining were performed to detect myocardial apoptosis; pathological sections of myocardium, serum lactate dehydrogenase (LDH) levels and Caspase-3 activity in myocardium were employed to evaluate myocardial injury of MI rats; echocardiography was utilized to assess cardiac function of rats. RESULTS We revealed that miR-431 expression was decreased in H2O2-treated H9c2 cells and myocardium of MI rats. The expression of Cleaved Caspase-3 (C-Caspase-3) in H9c2 cells treated with H2O2 was significantly increased, the cell viability was dramatically decreased, the apoptosis rate and the percentage of TUNEL positive cells were notably increased, but up-regulation of miR-431 could reverse these effects. At the same time, compared with the sham group, serum LDH levels were observably increased, myocardial Caspase-3 activity was also increased, and cardiac function was greatly reduced, while overexpression of miR-431 could reduce myocardial injury and improve cardiac function of MI rats. Through the Luciferase reporter gene experiment, we found that miR-431 could directly target HIPK3. CONCLUSIONS In summary, overexpression of miR-431 can inhibit apoptosis after myocardial infarction via targeting HIPK3, thereby reducing myocardial injury and improving cardiac function in MI rats.