title: Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress.
abstract: BACKGROUND
  Several clinical studies have demonstrated that levels of adiponectin are significantly reduced in patients with type 2 diabetes and that adiponectin levels are inversely related to the risk of myocardial ischemia. The present study was designed to determine the mechanism by which adiponectin exerts its protective effects against myocardial ischemia/reperfusion.
  
  
  RESULTS
  Adiponectin-/- or wild-type mice were subjected to 30 minutes of myocardial ischemia followed by 3 hours or 24 hours (infarct size and cardiac function) of reperfusion. Myocardial infarct size and apoptosis, production of peroxynitrite, nitric oxide (NO) and superoxide, and inducible NO synthase (iNOS) and gp91(phox) protein expression were compared. Myocardial apoptosis and infarct size were markedly enhanced in adiponectin-/- mice (P<0.01). Formation of NO, superoxide, and their cytotoxic reaction product, peroxynitrite, were all significantly higher in cardiac tissue obtained from adiponectin-/- than from wild-type mice (P<0.01). Moreover, myocardial ischemia/reperfusion-induced iNOS and gp91(phox) protein expression was further enhanced, but endothelial NOS phosphorylation was reduced in cardiac tissue from adiponectin-/- mice. Administration of the globular domain of adiponectin 10 minutes before reperfusion reduced myocardial ischemia/reperfusion-induced iNOS/gp91(phox) protein expression, decreased NO/superoxide production, blocked peroxynitrite formation, and reversed proapoptotic and infarct-enlargement effects observed in adiponectin-/- mice.
  
  
  CONCLUSIONS
  The present study demonstrates that adiponectin is a natural molecule that protects hearts from ischemia/reperfusion injury by inhibition of iNOS and nicotinamide adenine dinucleotide phosphate-oxidase protein expression and resultant oxidative/nitrative stress.
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
authors.forename: Erhe
authors.initials: E
authors.lastname: Gao
authors.forename: Xiangying
authors.initials: X
authors.lastname: Jiao
authors.forename: Yuexing
authors.initials: Y
authors.lastname: Yuan
authors.forename: Shuzhuang
authors.initials: S
authors.lastname: Li
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Christopher
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Lopez
authors.forename: Walter
authors.initials: W
authors.lastname: Koch
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Goldstein
authors.forename: Xin L
authors.initials: XL
authors.lastname: Ma
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D002316:Cardiotonic Agents; D008562:Membrane Glycoproteins; D026361:Reactive Nitrogen Species; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases