Adiponectin restores diabetic heart sensitivity to ischemic posctconditioning: role of STAT3 activation

Abstract

Diabetic hearts are prone to ischemia reperfusion (IR) injury and not sensitivity to ischemic postconditioning (IPostC) cardioprotection, and the mechanism is unclear. Adiponectin (APN) confers cardioprotection in non-diabetes by activating STAT3 (pSTAT3), a key protein in mediating IPostC protection. In diabetic heart, APN is decreased, together with reduced pSTAT3. We hypothesized APN may activate STAT3 in diabetic heart and restore its sensitivity to IPostC. Control (C) and Streptozotocin induced diabetic (D) rats were subjected to 30 min coronary artery ligation followed by 2 hours of reperfusion, without or with IPostC achieved by 3 episodes of 10s reperfusion and 10s re-occlusion at the onset of reperfusion. Rat was injected with APN (1x109pfu) 7 days before inducing IR. Cardiac functions were assessed by pressure volume (PV) conductance system. Post-ischemic myocardial infarct size was higher in D relative to C, together with significant reduction of cardiac pSTAT3 and reduction of end systolic PV relation,a reliable measure of ventricular systolic function, in D rats. All these changes in D were reverted by IPostC in the presence but not in the absence of APN (P<0.05 vs. D+APN+IPostC vs. D or D+APN), and abolished by AG490 (which inhibits STAT3 activation). It is concluded that APN restores diabetic heart sensitivity to IPostC by activating STAT3.