Haobo Li
The University of Hong Kong, Hong Kong
Title: Diabetes Abolishes Ischemic Postconditioning Cardioprotection by Impairing AdipoR1/Caveolin-3/STAT3 Signaling
Biography
Biography: Haobo Li
Abstract
Ischemic postconditioning (IPo) protects against myocardial ischemia reperfusion injury (MIRI) by activating signal transducer and activator of transcription 3 (STAT3) in non-diabetes, but lost its effectiveness in diabetes in which cardiac STAT3 activation is reduced concomitant with malfunction of adiponectin. Here, we found that IPo increased post-ischemic cardiomyocyte-derived adiponectin and enhanced mitochondrial STAT3 (mitoSTAT3) activation, and improved myocardial mitochondrial biogenesis and reduced oxidative stress, and eventually attenuated MIRI and improved cardiac functional recovery, in wild-type (WT) but not in adiponectin knockout (Adipo-/-) mice. Recombinant globular adiponectin (gAd) reversed the reduction of hypoxic postconditioning (HPo)-induced cardioprotective effects in cardiomyocytes isolated from Adipo-/- mice, but all these effects of adiponectin supplementation were abolished respectively by either specific STAT3 or adiponectin receptor 1(AdipoR1) gene knockdown, or caveolin-3 disruption. Adiponectin overexpression restored IPo cardioprotection by activating STAT3 in 4-week type-1 diabetic where AdipoR1 and Cav3 were functionally interactive, but not in 8-week diabetic rats whose cardiac caveolin-3 was severely reduced and AdipoR1/ caveolin-3 signaling impaired. Together, our data indicated that, under non-diabetic condition, IPo, by increasing cardiac adiponectin, activates mitoSTAT3 through AdipoR1/caveolin-3 to confer cardioprotection, while under diabetic condition, reduced adiponectin and impaired AdipoR1 and caveolin-3 interaction leads to the loss of IPo cardioprotection.