Cardioprotective effect of miRNA-22 on hypoxia/reoxygenation induced cardiomyocyte injury in neonatal rats

摘要

MicroRNAs (miRNAs) are implicated in the regulation of pathological and physiological processes in myocardial ischemia/reperfusion (MI/R). Recent studies have revealed that miR-22 might provide a potential cardioprotective effect on ischemic heart disease. However, the mechanism by which miR-22 prevents MI/R is still not fully clear. Here, we investigated the role of miR-22 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. MI/R was simulated in neonatal rat cardiomyocytes with 2 h hypoxia followed by 4 h reoxygenation. Prior to H/R, cells were transfected by Ad-miR-22 or Ad-scramble. It was revealed that H/R dramatically increased the release of CK and LDH, accompanied by a downregulation of miR-22 expression. Overexpression of miR-22 attenuated cardiomyocyte apoptosis and miR-22 target gene CREB binding protein (CBP) protein level, as determined by flow cytometry analysis and Western blot respectively. We further identified that miR-22 significantly inhibited CBP-related transcriptional factor AP-1 DNA binding activity under H/R. In addition, miR-22 could efficiently change Bcl-2/Bax ratio, and suppress the production of pro-inflammatory cytokines (TNF-a and IL-6) induced by H/R. In conclusion, these results suggest that miR-22 plays an important cardioprotective role partly via regulating CBP/AP-1 pathway to reduce cell apoptosis and inflammatory damage during MI/R injury.