Propofol‐mediated cardioprotection dependent of microRNA‐451/HMGB1 against myocardial ischemia‐reperfusion injury

Administration of propofol at the time of reperfusion has shown to protect the heart from ischemia and reperfusion (I/R) injury. The aim of the present study was to investigate the molecular mechanism underling the cardioprotective effect of propofol against myocardial I/R injury (MIRI) in vivo and in vitro. Rat heart I/R injury was induced by ligation of the left anterior descending (LAD) artery for 30 min followed by 2‐hr reperfusion. Propofol pretreatment (0.01 mg/g) was performed 10 min before reperfusion. In vitro MIRI was investigated in cultured cardiomyocytes H9C2 following hypoxia/reoxygenation (H/R) injuries. Propofol pretreatment in vitro was achieved in the medium supplemented with 25 μmol/L propofol before H/R injuries. Propofol pretreatment significantly increased miRNA‐451 expression, decreased HMGB1 expression, reduced infarct size, and I/R‐induced cardiomyocyte apoptosis in rat hearts undergoing I/R injuries. Knockdown of miRNA‐451 48 hr before I/R injury was found to increase HMGB1 expression, infarct size, and I/R‐induced cardiomyocyte apoptosis in rat hearts in the presence of propofol pretreatment. These in vivo findings were reproduced in vivo that knockdown of miRNA‐451 48 hr before H/R injuries increased HMGB1 expression and H/R‐induced apoptosis in cultured H9C2 supplemented with propofol. In addition, luciferase activity assays and gain‐of‐function studies found that propofol could decrease HMGB1, the target of miRNA‐541. Taken together our findings provide a first demonstration that propofol‐mediated cardioprotection against MIRI is dependent of microRNA‐451/HMGB1. The study provides a novel target to prevent I/R injury during propofol anesthesia. Taken together our findings provide a first demonstration that propofol‐mediated cardioprotection against MIRI is dependent of microRNA‐451/HMGB1. The study provides a novel target to prevent I/R injury during propofol anesthesia.