microRNA-22 attenuates myocardial ischemia-reperfusion injury via an anti-inflammatory mechanism in rats.

Previous studies have reported that microRNA-22 (miR-22) may be implicated in ischemia-reperfusion (I/R)-induced myocardial injury. Our previously published data also demonstrated that miR-22 may protect against myocardial I/R injury via anti-apoptosis in rats by targeting cAMP response element-binding protein binding protein (CBP). However, the specific function of miR-22 in myocardial I/R injury is far from fully elucidated. The present study was designed to investigate another cardioprotective signaling mechanism of miR-22 in myocardial I/R injury. A total of 40 adult male Sprague-Dawley rats were randomly divided into four equal groups (n=10): Sham, myocardial I/R, myocardial I/R with adenovirus expressing scramble miRNA (Ad-Scramble) and myocardial I/R with adenovirus expressing miR-22 (Ad-miR-22) groups. Besides the Sham operation group, the remaining three groups were artificially afflicted with coronary occlusion for 30 min and subsequently reperfused for 4 h. A light microscope was used to observe structural changes in the myocardium; reverse transcription polymerase chain reaction was used to measure the miR-22 mRNA expression level; the myocardial infarct size was analyzed by the Evans Blue/triphenyltetrazolium chloride double-staining; and p38 mitogen-activated protein kinase (MAPK), CBP, c-Jun-activator protein (AP)-1 and phospho (p)-c-Jun-AP-1 expression protein levels were detected by a western blot. Furthermore, ELISA was used to measure the levels of TNF-α and IL-6 in the myocardium. The results demonstrated that adenovirus-mediated miR-22 overexpression markedly reduced p38 MAPK, CBP, c-Jun-AP-1, p-c-Jun-AP-1 expression levels concomitant with an improvement in myocardial injury, including smaller infarct size, reduced release of creatine kinase, lactate dehydrogenase and proinflammation mediators (tumor necrosis factor-α and interleukin-6). These findings suggest that miR-22 has a protective effect on myocardial I/R injury. This protection mechanism, at least in part, is due to its anti-inflammatory function via the suppression of the p38 MAPK/CBP/c-Jun-AP-1 signaling pathway.