Document Detail

Increased Myocardial Ischemia/reperfusion Injury in Renal Failure Involves Cardiac Adiponectin Signal Deficiency.
MedLine Citation:
PMID:  24595307     Owner:  NLM     Status:  Publisher    
Plasma levels of adiponectin (APN) are significantly increased in patients with renal dysfunction and are inversely related to the risk of cardiovascular mortality. The present study was designed to determine the role of APN in myocardial ischemia/reperfusion (MI/R) injury in mice with renal failure, and delineate the underlying mechanisms. Renal failure was induced by subtotal nephrectomy (SN). Human recombinant globular domain of adiponectin (gAd) or full length adiponectin (fAd) was administered via intraperitoneal injection once daily for 7 consecutive days after SN and in vivo MI/R was introduced 3 weeks later. Both plasma and urinary levels of APN increased significantly in SN mice. Compared with sham-operated mice, cardiac function was significantly depressed and myocardial infarct size and apoptosis increased in SN mice following MI/R. The aggravated MI/R injury was further intensified in APN knockout mice and markedly ameliorated by treatment with gAd but not fAd. Moreover, SN increased myocardial NO metabolites, superoxide and their cytotoxic reaction product peroxynitrite, upregulated inducible NO synthase expression and decreased endothelial NOS phosphorylation. In addition, SN mice also exhibited reduced APN receptor-1 (AdipoR1) expression and AMPK activation. All these changes were further amplified in the absence of APN but reversed by gAd treatment. The present study demonstrates that renal dysfunction increases cardiac susceptibility to ischemic/reperfusion injury, which is associated with downregulated APN/AdipoR1/AMPK signaling and increased oxidative/nitrative stress in local myocardium, and provides the first evidence for the protective role of exogenous supplement of gAd on MI/R outcomes in renal failure.
Yanbin Song; Qiujun Yu; Junyi Zhang; Weidong Huang; Yi Liu; Haifeng Pei; Jingyi Liu; Lu Sun; Lu Yang; Congye Li; Yan Li; Fuyang Zhang; Ling Tao
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-3-4
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  -     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-3-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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