Exosomal miR‑152‑5p/ARHGAP6/ROCK axis regulates apoptosis and fibrosis in cardiomyocytes.

Acute myocardial infarction (AMI) is a fatal cardiovascular disease with a high mortality rate. The discovery of effective biomarkers is crucial for the diagnosis and treatment of AMI. In the present study, miRNA sequencing and reverse transcription-quantitative polymerase chain reaction techniques revealed that the expression of exosome derived miR-152-5p was significantly downregulated in patients with AMI compared with healthy controls. A series of functional validation experiments were then performed using H9c2 cardiomyocytes. Following transfection of the cardiomyocytes using an miR-152-5p inhibitor, immunofluorescence staining of a-smooth muscle actin revealed a marked increase in fibrosis. Western blotting revealed that the expression levels of the apoptotic protein Bax, TNF-α and collagen-associated proteins were significantly increased, whereas those of the apoptosis-inhibiting factor Bcl-2 and vascular endothelial growth factor A were significantly decreased. Furthermore, the binding of Rho GTPase-activating protein 6 (ARHGAP6) to miR-152-5p was predicted using an online database and verified using a dual-luciferase reporter gene assay. The transfection of cardiomyocytes with miR-152-5p mimics was found to inhibit the activation of ARHGAP6 and Rho-associated coiled-coil containing kinase 2 (ROCK2). These results suggest that miR-152-5p targets ARHGAP6 through the ROCK signaling pathway to inhibit AMI, which implies that miR-152-5p may be a diagnostic indicator and potential target for treatment of myocardial infarction.