Essential role of adiponectin in ischemic postconditioning cardioprotection and its association with signal transducer and activator of transcription 3

Abstract

Ischemic postconditioning (IPostC) protects the heart against ischemia reperfusion injury (IRI) by activating signal transducer and activator of transcription 3 (STAT3). Adiponectin (APN), a protein with anti-IRI property, activates STAT3 (Cell Metab. 2011, 13: 401-12), but its role in IPostC is unknown. We postulated that APN is essential for IPostC to confer cardioprotection. Wild type (WT) and APN knockout (KO) mice were subjected to 30 min coronary occlusion followed by 120 min reperfusion without or with IPostC achieved by 3 cycles of 10s of ischemia/10s of reperfusion. Cardiac function was assessed by pressure-volume (PV) loop system. At the end of reperfusion, KO mice displayed larger infarct size and higher plasma creatine kinase-MB, but lower end-systolic PV relation (a reliable measure of ventricular function) and dP/dt (all P<0.05, vs. WT). IPostC significantly attenuated all these changes and increased phosphorylations of cardiac STAT3 (at Ser727), Akt (at Ser473) and eNOS in WT but not in KO mice. In cultured H9C2 cells exposed to 60 min hypoxia (H)/120 min reoxygenation (R), gene silencing with APN or STAT3 siRNA all abolished hypoxic postconditioning (HPostC, 3 cycles of 5 min H/5 min R) mediated cell protection. APN supplementation restored HPostC protection in APN siRNA treated but not in STAT3 siRNA treated cells. We conclude that APN is a key protein for IPostC to activate STAT3 to confer protection.