Oxidative stress regulates cardiomyocyte energy metabolism through the IGF2BP2-dynamin2 signaling pathway

Over the past few decades, numerous clinical and experimental studies have confirmed that oxidative stress is enhanced in heart failure (HF). We recently found that inhibition of highly expressed dynamin2 can protect myocardial ischemia-reperfusion injury in mice and inhibit oxidative stress in ischemic cardiomyocytes. However, the specific mechanisms are still not fully understood. In this study, we hypothesized that oxidative stress induces cardiomyocyte apoptosis through IGF2BP2 regulation, which is regulated through the dynamin2 expression.

H2O2-treated cardiomyocytes were observed for the regulatory effect of reactive oxygen species (ROS) on IGF2BP2 and the effect of IGF2BP2 on dynamin2 gene expression was determined by lentiviral-mediated IGF2BP2 overexpression. Then, siRNA knockdown of dynamin2 was used to observe whether it can alter the effect of IGF2BP2 on myocardial cells. Finally, IGF2BP2 was knocked down in ischemic rats using shRNA to determine the effects of IGF2BP2 on myocardial ischemia.

ROS can promote dynamin2 expression by inducing IGF2BP2 expression and dynamin2 knockdown could reduce the injury of IGF2BP2 to cardiomyocytes. Inhibition of IGF2BP2 expression in myocardial ischemic rats ameliorated cardiac fibrosis in ischemic myocardium.

Oxidative stress can induce cardiomyocyte apoptosis through the IGF2BP2-dynamin2 pathway. Inhibition of IGF2BP2 expression significantly improves the fibrosis and remodeling that occurs in ischemic myocardium.