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- Title
Hyperglycemia Abrogates Ischemic Postconditioning Cardioprotection by Impairing AdipoR1/Caveolin-3/STAT3 Signaling in Diabetic Rats.
- Authors
Haobo Li; Weifeng Yao; Zipeng Liu; Aimin Xu; Yu Huang; Xin-liang Ma; Irwin, Michael G.; Zhengyuan Xia; Li, Haobo; Yao, Weifeng; Liu, Zipeng; Xu, Aimin; Huang, Yu; Ma, Xin-Liang; Xia, Zhengyuan
- Abstract
Signal transducer and activator of transcription 3 (STAT3) activation is key for ischemic postconditioning (IPo) to attenuate myocardial ischemia-reperfusion injury (MIRI), but IPo loses cardioprotection in diabetes in which cardiac STAT3 activation is impaired and adiponectin (APN) reduced. We found that IPo increased postischemic cardiomyocyte-derived APN, activated mitochondrial STAT3 (mitoSTAT3), improved mitochondrial function, and attenuated MIRI in wild-type but not in APN knockout (Adipo(-/-)) mice subjected to 30 min coronary occlusion, followed by 2 or 24 h of reperfusion. Hypoxic postconditioning-induced protection against hypoxia/reoxygenation injury was lost in Adipo(-/-) cardiomyocytes but restored by recombinant APN, but this APN beneficial effect was abolished by specific STAT3 or APN receptor 1 (AdipoR1) gene knockdown, or caveolin-3 (Cav3) disruption. APN activated cardiac STAT3 and restored IPo cardioprotection in 4-week diabetic rats where AdipoR1 and Cav3 were functionally interactive but not in 8-week diabetic rats whose cardiac Cav3 was severely reduced and AdipoR1/Cav3 signaling impaired. We concluded that IPo activates mitoSTAT3 through APN/AdipoR1/Cav3 pathway to confer cardioprotection, whereas in diabetes, IPo loses cardioprotection due to impaired APN/AdipoR1/Cav3 signaling. Therefore, effective means that may concomitantly activate APN and repair APN signaling (i.e., AdipoR1/Cav3) in diabetes may represent promising avenues in the treatment of MIRI in diabetes.
- Subjects
HYPERGLYCEMIA; CAVEOLINS; STAT proteins; ADIPONECTIN; DIABETES; LABORATORY rats; DIABETES complications; HEART metabolism; ANIMAL experimentation; CARRIER proteins; CELL receptors; CELLULAR signal transduction; CORONARY arteries; MICE; MYOCARDIAL reperfusion complications; RATS; THERAPEUTICS; DISEASE complications; PREVENTION
- Publication
Diabetes, 2016, Vol 65, Issue 4, p942
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db15-0782