Proteinase-activated receptor 2 deficiency is a protective factor against cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury

Abstract

Previous studies have established that proteinaseactivated receptor 2 (PAR 2) activation protects against myocardial ischemia/reperfusion injury (MI/RI). However, the role of PAR 2 deficiency in MI/RI remains unclear. The aim of the present study was to examine the effect of PAR2 deficiency on cardiomyocyte apoptosis and to clarify the potential molecular mechanisms for its protective effect against MI/RI. Using a mouse model of MI/RI, cardiac function was evaluated by echocardiography, infarct size was assessed by triphenyltetrazolium chloride staining, and myocardial cell apoptosis was measured by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling staining. Annexin V/propidium iodide staining, and expression of Bcl-2 and cleaved PAR P were determined to assess apoptosis in myocardial H9c2 cells exposed to hypoxia/reoxygenation (H/R) injury-simulating MI/RI. Phosphorylated ER K1/2, JNK, and p38 MAPK protein expression levels were analyzed by western blotting. The findings indicated that PAR 2 deficiency markedly reduced cardiomyocyte apoptosis in the MI/RI mouse model, as well as in myocardial H9c2 cells exposed to H/R. Furthermore, PAR 2 knockdown clearly prevented phosphorylation of ER K1/2 and JNK in myocardial H9c2 cells. The results revealed that PAR2 deficiency alleviated MI/RI- associated apoptosis by inhibiting phosphorylation of ER K1/2 and JNK. Therefore, targeted PAR 2 silencing may be a potential therapeutic approach for alleviation of MI/RI.