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

Abstract

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.

Research Advances of Engineered Exosomes as Drug Delivery Carrier

“…Cardiovascular disease is a type of disease involving the heart and blood vessels that is high fatality rate and difficult to treat. , Cardiomyocytes, vascular cells, and fibroblasts release exosomes in the heart with low immunogenicity, and cardiac exosomal miRNAs are able to regulate the expression of sarcomeric genes, antifibrotic activity, and angiogenesis. − The modification of natural exosomes into engineered exosomes by bioengineering technology can not only optimize its various biological functions, but also compensate for the weak targeting ability and low drug loading efficiency of natural exosomes. It has been shown that genetic modification of engineered exosomes loaded with miR-425 and miR-744 can target the TGF-β pathway to inhibit angiotensin-induced collagen and fibrin synthesis as a way to inhibit myocardial remodeling .…”