Abstract
This study aims to investigate the effect and the related mechanisms of bromodomain-containing protein 4 (BRD4) inhibition on myocardial ischemia/reperfusion (I/R) injury. In vivo and in vitro myocardial I/R models were constructed. Expression of BRD4 was examined by RT-qPCR and Western blot. I/R injury was evaluated by analyzing cardiac function and the activity of biochemical markers of myocardial injury. Inflammation and oxidative stress were determined by measuring the levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and superoxide dismutase. The activation of the PI3K/AKT signaling pathway was tested by the phosphorylation of p85 and AKT. We found BRD4 was significantly increased in the myocardial tissues after myocardial I/R injury. BRD4 inhibition suppressed the indices of cardiac function and the biochemical markers of myocardial injury. I/R-induced inflammation and oxidative stress were suppressed by shBRD4 in vivo and in vitro. In addition, BRD4 inhibition significantly increased the relative protein expression levels of p-p85, p-AKT T308, and p-AKT S473. In conclusion, this study for the first time demonstrated the protective effect of BRD4 inhibition on myocardial I/R injury in vivo and in vitro, and this effect was related to the suppression of inflammation and oxidative stress through the activation of the PI3K/AKT signaling pathway.