title: Increased myocardial ischemia-reperfusion injury in renal failure involves cardiac adiponectin signal deficiency.
abstract: 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 wk 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.
authors.affiliation: Department of Cardiology and.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Song
authors.forename: Qiujun
authors.initials: Q
authors.lastname: Yu
authors.forename: Junyi
authors.initials: J
authors.lastname: Zhang
authors.forename: Weidong
authors.initials: W
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Haifeng
authors.initials: H
authors.lastname: Pei
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Congye
authors.initials: C
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Fuyang
authors.initials: F
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Qu
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000378:metabolism / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D026361:Reactive Nitrogen Species / Q000502:physiology; D054419:Receptors, Adiponectin / Q000378:metabolism; D051437:Renal Insufficiency / Q000150:complications* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D026361:Reactive Nitrogen Species; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; D055372:AMP-Activated Protein Kinases
keywords: adiponectin; oxidative/nitrative stress; renal failure; subtotal nephrectomy