Propofol post-conditioning confers ischemic cardioprotection via HO-1/STAT3 signaling: role of peroxynitrite

Abstract

Propofol, an aesthetic with antioxidant and peroxynitrite (ONOO–) scavenging property, when given during reperfusion attenuates myocardial ischemia/reperfusion (MI/R) injury. Heme oxygenase-1 (HO-1) and STAT3 are key proteins in postconditioning (PC) cardioprotection. We explored if Propofol PC (PPC) confers cardioprotection by scavenging ONOO– and activating the HO-1/STAT3 pathway. Rats were subjected to 30 min coronary artery occlusion and 120 min reperfusion in vivo. Rats (n=7/group) were respectively treated with Propofol (2mg/kg), IPC, ONOO– generator SIN-1(1.5 mg/kg), ONOO– scavenger FeTPPS (10 mg/kg) during MI/R. Also, primarily cultured cardiomyocytes were subjected to hypoxia/re-oxygenation in the absence or presence of SIN-1 or FeTPPS. PPC conferred similar cardioprotection to IPC in reducing postischemic myocardial infarction compared to control. FeTPPS enhanced PPC cardioprotection while SIN-1 abolished PPC cardioprotection. HO-1 and p-STAT3 protein expression was increased in PPC group compared to control and it was associated with decreased ONOO– production and increased antioxidant capacity. PPC also attenuated post-hypoxic lactate dehydrogenase in vitro. However, HO-1/STAT3 gene knockdown abolished protective effect of PPC. In conclusion, PPC confers cardioprotection by scavenging ONOO– and activating the HO-1/STAT3 pathway.