title: Coronary and aortic endothelial function affected by feedback between adiponectin and tumor necrosis factor α in type 2 diabetic mice.
abstract: OBJECTIVE
  To verify that adiponectin and tumor necrosis factor (TNF)-α reciprocally regulate their expression, thereby synergistically affecting both coronary and aortic endothelial dysfunction in type 2 diabetic mice.
  
  
  RESULTS
  We examined endothelium-dependent and endothelium-independent vasodilation/vasorelaxation of coronary arterioles and aortas in control mice, diabetic mice (Lepr(db)), and Lepr(db) treated with adiponectin or neutralizing antibody to TNF-α (anti-TNF-α). Endothelium-dependent vasodilation to acetylcholine in both coronary arterioles and aortas was blunted in Lepr(db) compared with control mice. Endothelium-independent vasodilation to sodium nitroprusside was comparable. Adiponectin and anti-TNF-α improved acetylcholine-induced vasodilation of coronary arterioles and aortas in Lepr(db) without affecting dilator response to sodium nitroprusside. Adiponectin protein expression was significantly reduced, and TNF-α protein expression was significantly greater, in coronary arterioles and aortas of Lepr(db) compared with control mice. Immunofluorescence staining results indicate that adiponectin was colocalized with endothelial cells. Anti-TNF-α treatment upregulated adiponectin protein expression in Lepr(db) coronary arterioles and aortas. Adiponectin administration reduced TNF-α protein expression in Lepr(db). Although adiponectin receptor 1 protein expression in coronary arterioles and aortas was similar between control and diabetic mice, adiponectin receptor 2 protein expression was significantly reduced in Lepr(db). Both adiponectin and anti-TNF-α inhibited IκBα phosphorylation and nuclear factor κB protein expression in Lepr(db), suggesting that adiponectin and TNF-α signaling may converge on nuclear factor κB to reciprocally regulate their expression.
  
  
  CONCLUSIONS
  A reciprocal suppression occurs between adiponectin and TNF-α that fundamentally affects the regulation of coronary and aortic endothelial function in type 2 diabetic mice.
authors.affiliation: Department of Internal Medicine, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Hanrui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yoonjung
authors.initials: Y
authors.lastname: Park
authors.forename: Cuihua
authors.initials: C
authors.lastname: Zhang
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D025461:Feedback, Physiological; D008297:Male; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D052242:Adiponectin; D000911:Antibodies, Monoclonal; D002317:Cardiovascular Agents; D014409:Tumor Necrosis Factor-alpha
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