title: Effects of Obesity on Perivascular Adipose Tissue Vasorelaxant Function: Nitric Oxide, Inflammation and Elevated Systemic Blood Pressure.
abstract: BACKGROUND
  Perivascular adipose tissue (PVAT) surrounds most vessels in the human body. Healthy PVAT has a vasorelaxant effect which is not observed in obesity. We assessed the contribution of nitric oxide (NO), inflammation and endothelium to obesity-induced PVAT damage.
  
  
  METHODS
  Rats were fed a high-fat diet or normal chow. PVAT function was assessed using wire myography. Skeletonised and PVAT-intact mesenteric vessels were prepared with and without endothelium. Vessels were incubated with L-NNA or superoxide dismutase (SOD) and catalase. Gluteal fat biopsies were performed on 10 obese and 10 control individuals, and adipose tissue was assessed using proteomic analysis.
  
  
  RESULTS
  In the animals, there were significant correlations between weight and blood pressure (BP; r = 0.5, p = 0.02), weight and PVAT function (r = 0.51, p = 0.02), and PVAT function and BP (r = 0.53, p = 0.01). PVAT-intact vessel segments from healthy animals constricted significantly less than segments from obese animals (p < 0.05). In a healthy state, there was preservation of the PVAT vasorelaxant function after endothelium removal (p < 0.05). In endothelium-denuded vessels, L-NNA attenuated the PVAT vasorelaxant function in control vessels (p < 0.0001). In obesity, incubation with SOD and catalase attenuated PVAT-intact vessel contractility in the presence and absence of endothelium (p < 0.001). In obese humans, SOD [Cu-Zn] (SOD1; fold change -2.4), peroxiredoxin-1 (fold change -2.15) and adiponectin (fold change -2.1) were present in lower abundances than in healthy controls.
  
  
  CONCLUSIONS
  Incubation with SOD and catalase restores PVAT vasorelaxant function in animal obesity. In the rodent model, obesity-induced PVAT damage is independent of endothelium and is in part due to reduced NO bioavailability within PVAT. Loss of PVAT function correlates with rising BP in our animal obesity model. In keeping with our hypothesis of inflammation-induced damage to PVAT function in obesity, there are lower levels of SOD1, peroxiredoxin-1 and adiponectin in obese human PVAT.
authors.affiliation: Institute of Cardiovascular Sciences, The University of Manchester, Manchester, UK.
authors.forename: Reza
authors.initials: R
authors.lastname: Aghamohammadzadeh
authors.forename: Richard D
authors.initials: RD
authors.lastname: Unwin
authors.forename: Adam S
authors.initials: AS
authors.lastname: Greenstein
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Heagerty
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D019899:Paracrine Communication / Q000187:drug effects; D054464:Peroxiredoxins / Q000378:metabolism; D040901:Proteomics; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; C000606290:SOD1 protein, human; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D019001:Nitric Oxide Synthase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1