title: Effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity.
abstract: OBJECTIVE
  The aim of this study was to investigate the effects of bariatric surgery on small artery function and the mechanisms underlying this.
  
  
  BACKGROUND
  In lean healthy humans, perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arteries, but this is lost in obesity-associated conditions such as the metabolic syndrome and type II diabetes where there is evidence of adipocyte inflammation and increased oxidative stress.
  
  
  METHODS
  Segments of small subcutaneous artery and perivascular fat were harvested from severely obese individuals before (n = 20) and 6 months after bariatric surgery (n = 15). Small artery contractile function was examined in vitro with wire myography, and perivascular adipose tissue (PVAT) morphology was assessed with immunohistochemistry.
  
  
  RESULTS
  The anticontractile activity of PVAT was lost in obese patients before surgery when compared with healthy volunteers and was restored 6 months after bariatric surgery. In vitro protocols with superoxide dismutase and catalase rescued PVAT anticontractile function in tissue from obese individuals before surgery. The improvement in anticontractile function after surgery was accompanied by improvements in insulin sensitivity, serum glycemic indexes, inflammatory cytokines, adipokine profile, and systolic blood pressure together with increased PVAT adiponectin and nitric oxide bioavailability and reduced macrophage infiltration and inflammation. These changes were observed despite the patients remaining severely obese.
  
  
  CONCLUSIONS
  Bariatric surgery and its attendant improvements in weight, blood pressure, inflammation, and metabolism collectively reverse the obesity-induced alteration to PVAT anticontractile function. This reversal is attributable to reductions in local adipose inflammation and oxidative stress with improved adiponectin and nitric oxide bioavailability.
authors.affiliation: Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom; Manchester Wellcome Trust Clinical Research Facility, Manchester, United Kingdom. Electronic address: reza.zadeh@manchester.ac.uk.
authors.forename: Reza
authors.initials: R
authors.lastname: Aghamohammadzadeh
authors.affiliation: Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom; Manchester Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Greenstein
authors.affiliation: Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom; Manchester Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Rahul
authors.initials: R
authors.lastname: Yadav
authors.affiliation: Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Jeziorska
authors.affiliation: Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom; Manchester Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Salam
authors.initials: S
authors.lastname: Hama
authors.affiliation: Manchester Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Fardad
authors.initials: F
authors.lastname: Soltani
authors.affiliation: Manchester Wellcome Trust Clinical Research Facility, Manchester, United Kingdom; Department of Clinical Biochemistry, Manchester Royal Infirmary, Manchester, United Kingdom.
authors.forename: Phil W
authors.initials: PW
authors.lastname: Pemberton
authors.affiliation: Salford Royal NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Basil
authors.initials: B
authors.lastname: Ammori
authors.affiliation: Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom; Manchester Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
authors.affiliation: Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom; Manchester Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Handrean
authors.initials: H
authors.lastname: Soran
authors.affiliation: Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom; Manchester Wellcome Trust Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Heagerty
mesh_terms: D017667:Adipocytes / Q000473:pathology*; D054392:Adipokines / Q000097:blood; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000473:pathology; D001158:Arteries / Q000502:physiology*; D050110:Bariatric Surgery; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D002374:Catalase / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D016166:Free Radical Scavengers / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000032:analysis; D038321:Glycemic Index; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology; D020738:Leptin / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000601:surgery; D052243:Resistin / Q000097:blood; D040521:Subcutaneous Tissue / Q000098:blood supply; D013482:Superoxide Dismutase / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D054392:Adipokines; D052242:Adiponectin; D001786:Blood Glucose; D002097:C-Reactive Protein; D002374:Catalase; D016207:Cytokines; D016166:Free Radical Scavengers; D006442:Glycated Hemoglobin; D007328:Insulin; D020738:Leptin; D009569:Nitric Oxide; D009638:Norepinephrine; D052243:Resistin; D013482:Superoxide Dismutase; D014662:Vasoconstrictor Agents; C517652:hemoglobin A1c protein, human