Abstract
Myocardial ischemia/reperfusion (I/R) injury is a common cardiovascular disease with high morbidity and mortality globally, which derives from acute myocardial infarction and coronary artery disease. Elabela has been proved to bind to apelin receptors in the heart. The present study aimed to investigate the protective effects of Elabela in myocardial I/R injury and illustrating the potential mechanisms. In this study, the rat I/R model was established in vivo. Following treatment with Elabela, the histopathological changes of heart tissue were evaluated by the hematoxylin and eosin- or Masson's trichrome staining. Apoptosis of heart tissue was examined using TUNEL staining. The expression of type I or III collagen and apoptosis-associated proteins was measured using western blotting. Moreover, myocardial ultrastructure in myocardium was detected via electron microscopy analysis. H9c2 cells were treated with hypoxia/reoxygenation (H/R) to mimic the myocardial I/R injury in vitro. After treatment with Elabela or Elabela combined with LY294002, the levels of oxidative stress and apoptosis were examined. The results revealed that Elabela significantly improved the pathological changes of rat myocardial tissues induced by I/R. Additionally, Elabela treatment reduced cardiomyocyte I/R induced fibrosis and apoptosis as well as ameliorated mitochondrial dysfunction in animal and cells. Within inhibition of PI3K pathway, the protective effects of Elabela was reversed. Taken together, these findings demonstrated that Elabela could protect against fibrosis, apoptosis and oxidative stress via PI3K/ATK signaling pathway in cardiac ischemia reperfusion.