Apelin-13 ameliorates myocardial ischemia/reperfusion injury by modulating macrophage polarization

Macrophage polarization plays a crucial role in myocardial ischemia/reperfusion (I/R) injury. Although Apelin-13 is known for its anti-inflammatory effects, its impact on macrophage polarization during myocardial I/R injury remains unclear. This study aimed to investigate the effects of Apelin-13 on macrophage polarization and cardiac function in a rat I/R model and H9c2 cells in vitro. I/R injury was induced by ligating the left anterior descending coronary artery with reperfusion times of 2 h and 7 days. H9c2 cells and peritoneal macrophages were cultured in vitro. We show that Apelin-13 significantly improves cardiac function and reduces infarct size in a rat I/R model, as evidenced by improved hemodynamic and echocardiographic parameters. Apelin-13 treatment decreased myocardial apoptosis by modulating the Bcl-2/Bax ratio and shifted macrophage polarization from the pro-inflammatory M1 phenotype to the reparative M2 phenotype in vivo. In vitro, Apelin-13 suppressed LPS-induced pro-inflammatory cytokine production and promoted M2 markers in rat peritoneal macrophages. Furthermore, conditioned medium from Apelin-13-treated macrophages enhanced H9c2 cell survival following oxygen-glucose deprivation/reoxygenation. These findings suggest Apelin-13 as a promising therapeutic strategy for myocardial I/R injury by modulating macrophage polarization and reducing cardiomyocyte apoptosis.