Authors

Wei Yi, Department of Emergency Medicine, Thomas Jefferson University; Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xian, P.R. China
Yang Sun, Department of Emergency Medicine, Thomas Jefferson University; Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xian, P.R. China
Erhe Gao, Center for Translational Medicine, Thomas Jefferson UniversityFollow
Xufeng Wei, Department of Emergency Medicine, Thomas Jefferson University; Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xian, P.R. China
Wayne Bond Lau, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Qijun Zheng, Department of Emergency Medicine, Thomas Jefferson University; Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xian, P.R. China
Yajing Wang, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Yuexing Yuan, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Xiaoliang Wang, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Ling Tao, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xian, P.R. China
Rong Li, Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xian, P.R. China
Walter Koch, Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xian, P.R. ChinaFollow
Xin-Liang Ma, Department of Emergency Medicine, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

10-1-2011

Comments

This article has been peer reviewed and is published in Antioxidants & Redox Signaling Volume 15, Issue 7, 1 October 2011, Pages 1779-1788. The published version is available at DOI: 10.1089/ars.2010.3722. ©Mary Ann Liebert, Inc

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Abstract

Diabetes exacerbates ischemic heart disease morbidity and mortality via incompletely understood mechanisms. Although adiponectin (APN) reduces myocardial ischemia/reperfusion (MI/R) injury in nondiabetic animals, whether APN's cardioprotective actions are altered in diabetes, a pathologic condition with endogenously reduced APN, has never been investigated. High-fat diet (HD)-induced diabetic mice and normal diet (ND) controls were subjected to MI via coronary artery ligation, and given vehicle or APN globular domain (gAPN, 2 μg/g) 10 min before reperfusion. Compared to ND mice (where gAPN exerted pronounced cardioprotection), HD mice manifested greater MI/R injury, and a tripled gAPN dose was requisite to achieve cardioprotective extent seen in ND mice (i.e., infarct size, apoptosis, and cardiac function). APN reduces MI/R injury via AMP-activated protein kinase (AMPK)-dependent metabolic regulation and AMPK-independent antioxidative/antinitrative pathways. Compared to ND, HD mice manifested significantly blunted gAPN-induced AMPK activation, basally and after MI/R (p<0.05). Although both low- and high-dose gAPN equally attenuated MI/R-induced oxidative stress (i.e., NADPH oxidase expression and superoxide production) and nitrative stress (i.e., inducible nitric oxide synthase expression, nitric oxide production, and peroxynitrite formation) in ND mice, only high-dose gAPN efficaciously did so in HD mice. We demonstrate for the first time that HD-induced diabetes diminished both AMPK-dependent and AMPK-independent APN cardioprotection, suggesting an unreported diabetic heart APN resistance.

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