title: Mechanisms of increased vascular superoxide production in human varicose veins.
abstract: BACKGROUND
  Varicose vein disease is one of the most common morbidities in the developed countries. Recent studies have shown that oxidative stress is increased in varicose veins (VV) and venous insufficiency. However, the exact mechanisms of oxidative stress in VV remain unknown.
  
  
  OBJECTIVE
  The aim of the study was to measure superoxide anion production and analyze its enzymatic sources in VV in comparison with control human saphenous veins (HSV). Superoxide production was also compared between the proximal and distal segments of the veins.
  
  
  METHODS
  Proximal and distal segments of varicose veins (14 patients, aged 52 ±3.5 years) and control veins (15 patients, aged 56 ±4 years) were obtained during VV removal or elective coronary artery bypass graft surgery, respectively. Subjects were matched for age, sex, and the major risk factors for atherosclerosis. Superoxide was measured by lucigenin-enhanced chemiluminescence (5 μmol/l) in the presence and absence of oxidase inhibitors.
  
  
  RESULTS
  Superoxide production was increased in VV compared with control HSV. This increase was particularly evident in the distal segments of VV. There was a significant correlation between superoxide production in the proximal and distal segments of HSV but not of VV. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and uncoupled nitric oxide synthase (NOS) were the major sources of superoxide in VV, because their inhibitors greatly attenuated superoxide production in VV.
  
  
  CONCLUSIONS
  NADPH oxidases and NOS could represent valuable drug targets for pharmacological treatment and prevention of varicose vein disease. Oxidative stress may provide a link between endothelial dysfunction, inflammation, and immune activation and the development of chronic venous dysfunction.
authors.affiliation: Department of Internal and Agricultural Medicine, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Guzik
authors.forename: Maciej
authors.initials: M
authors.lastname: Chwała
authors.forename: Paweł
authors.initials: P
authors.lastname: Matusik
authors.forename: Dominik
authors.initials: D
authors.lastname: Ludew
authors.forename: Dominik
authors.initials: D
authors.lastname: Skiba
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wilk
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mrowiecki
authors.forename: Bogdan
authors.initials: B
authors.lastname: Batko
authors.forename: Andrzej
authors.initials: A
authors.lastname: Cencora
authors.forename: Bogusław
authors.initials: B
authors.lastname: Kapelak
authors.forename: Jerzy
authors.initials: J
authors.lastname: Sadowski
authors.forename: Ryszard
authors.initials: R
authors.lastname: Korbut
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Guzik
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D012501:Saphenous Vein / Q000201:enzymology*; D013481:Superoxides / Q000378:metabolism*; D014648:Varicose Veins / Q000201:enzymology*; D014689:Venous Insufficiency / Q000201:enzymology*
chemical_list: D013481:Superoxides; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases