Rosuvastatin Alleviates Ischemia/Reperfusion Injury in Cardiomyocytes by Downregulating Hsa-miR-24-3p to Target Upregulated Uncoupling Protein 2.

Abstract

Statins could reduce the risks of coronary heart disease death and ischemic cardiovascular events. In this study, we aim to explore the role of rosuvastatin in ischemia/reperfusion (I/R)-injured cardiomyocytes and the possible mechanism. An I/R model was established by oxygen-glucose deprivation/reperfusion (OGD/R). The protective effects of rosuvastatin pretreatment on OGD/R-injured cardiomyocytes were performed using MTT assay, lactate dehydrogenase (LDH) release assay, and quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics software TargetScan and miRTarBase were used to predict the targeted miRNAs with uncoupling protein (UCP)2. Furthermore, verify the binding capacity of hsa-miR-24-3p and UCP2 with qRT-PCR and dual-luciferase reporter assay. The expression of UCP2, cell viability, LDH level, and apoptosis level affected by downregulated hsa-miR-24-3p were assessed using qRT-PCR, western blotting, MTT, the LDH kit, and flow cytometry. Pretreatment with rosuvastatin could significantly augment cell viability, reduce LDH level, increase the expression of UCP2, and downregulate hsa-miR-24-3p in OGD/R-injured H9c2 cells. miR-24-3p was closely connected with UCP2, and downregulated miR-24-3p could promote UCP2 expression, which presented cell viability increasing, LDH release and cell apoptosis inhibition in OGD/R condition. Moreover, it decreased the protein expression of Cleaved-Caspase-9 and Cyto C. This is the first time our study suggests that rosuvastatin pretreatment protects cardiomyocytes from OGD/R through upregulating UCP2 through downregulation of hsa-miR-24-3p.