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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2013, Vol. 7 Issue (3) : 301-305     DOI: 10.1007/s11684-013-0283-1
REVIEW |
Adiponectin: mechanisms and new therapeutic approaches for restoring diabetic heart sensitivity to ischemic post-conditioning
Tingting Wang1,2(), Shanglong Yao1, Zhengyuan Xia2(), Michael G. Irwin2
1. Department of Anesthesiology and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; 2. Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China
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Abstract  

Systemic inflammatory response following myocardial ischemia-reperfusion injury (IRI) to a specific organ may cause injuries. Ischemic post-conditioning (IPostC) has emerged as a promising method for myocardial protection against IRI both in experimental and in clinical settings. Enhancement of endogenous nitric oxide (NO) is one of the major mechanisms by which IPostC confers cardioprotection. However, the sensitivity of the diabetic heart to IPostC is impaired and the underlying mechanism is unknown. Adiponectin (APN) is an adipocyte-derived plasma protein with anti-diabetic and anti-inflammatory properties. Plasma levels of APN are decreased in obese subjects and in patients with type 2 diabetes. APN supplementation has been shown to increase NO production and attenuate myocardial IRI in normal (non-diabetic) animals. However, the effect of APN on myocardial injury in diabetic subjects, especially its potential in restoring the sensitivity of the diabetic heart to IPostC has not been investigated. In the current paper, we discussed the possible reasons why the myocardium of diabetic subjects loses sensitivity to IPostC and also highlighted the potential effectiveness and mechanism of APN in restoring IPostC cardioprotection in diabetes. This review proposes to conduct studies that may facilitate the development of novel and optimal therapies to enhance cardioprotection in patients with severe diseases such as diabetes.

Keywords adiponectin      ischemic post-conditioning      ischemia reperfusion injury      diabetes     
Corresponding Authors: Wang Tingting,Email:wangtingting721@yahoo.com; Xia Zhengyuan,Email:zyxia@hku.hk   
Issue Date: 05 September 2013
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-013-0283-1     OR     http://academic.hep.com.cn/fmd/EN/Y2013/V7/I3/301
Fig.1  Schematic representation of the proposed mechanism for restoration of diabetic heart sensitivity to ischemic post-conditioning by adiponectin supplementation. Tumor necrosis factor-alpha (TNF-α) at low concentrations binds to TNF-α receptor-2 which activates in sequence JAK and STAT-3, confering cardioprotection via the SAFE pathway. Although cross-talk may exist between the RISK and SAFE pathways, ischemic post-conditioning can trigger SAFE pathway independent of its ability to activate the classic RISK pathway. Adiponectin may activate the SAFE pathway by stimulating endothelial NO production and subsequent TNF production. Adiponectin can also activate AMPK which may trigger JAK/STAT-3 signaling. On the other hand, AMPK can directly activate eNOS and inhibit iNOS. The resulting increase in nitric oxide bioavailability then confers cardioprotection.
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