title: Uncoupling protein-2 protects endothelial function in diet-induced obese mice.
abstract: BACKGROUND
  Previous studies indicate uncoupling protein-2 (UCP2) as an antioxidant defense against endothelial dysfunction in hypertension. UCP2 also regulates insulin secretion and action. However, the role of UCP2 in endothelial dysfunction associated with diabetes and obesity is unclear.
  
  
  OBJECTIVE
  UCP2 protects against endothelial dysfunction induced by high-fat diet through inhibition of reactive oxygen species (ROS) production, and subsequent increase of nitric oxide bioavailability.
  
  
  RESULTS
  Endothelium-dependent relaxation (EDR) in aortae and mesenteric arteries in response to acetylcholine was measured in wire myograph. Flow-mediated vasodilatation in 2(nd)-order mesenteric arteries was measured in pressure myograph. ROS production is measured by CM-H(2)DCFDA and DHE fluorescence. High-glucose exposure reduced EDR in mouse aortae, which was exaggerated in UCP2 knockout (KO) mice, whereas UCP2 overexpression by adenoviral infection (AdUCP2) restored the impaired EDR. Impairment of EDR and flow-mediated vasodilatation in aortae and mesenteric arteries from high-fat diet-induced obese mice (DIO) was exaggerated in UCP2KO DIO mice compared with wild-type DIO littermates, whereas AdUCP2 i.v. injection restored both EDR and flow-mediated vasodilatation in DIO mice. Improved EDR in mesenteric arteries was inhibited by nitric oxide synthase inhibitor. UCP2 overexpression also inhibited intracellular ROS production in the en face endothelium of aorta and mesenteric artery of DIO mice, whereas UCP2 deficiency enhanced ROS production.
  
  
  CONCLUSIONS
  UCP2 preserves endothelial function through increasing nitric oxide bioavailability secondary to the inhibition of ROS production in the endothelium of obese diabetic mice.
authors.affiliation: Institute of Vascular Medicine, Hong Kong SAR, China.
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Tian
authors.forename: Wing Tak
authors.initials: WT
authors.lastname: Wong
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Ye
authors.initials: Y
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Wai San
authors.initials: WS
authors.lastname: Cheang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009213:Myography; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009924:Organ Culture Techniques; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012039:Regional Blood Flow; D013997:Time Factors; D014162:Transfection; D000071246:Uncoupling Protein 2; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005947:Glucose