title: Reduced nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide and vascular endothelial dysfunction in human heart failure.
abstract: OBJECTIVE
  We investigated the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in endothelial dysfunction in human heart failure.
  
  
  BACKGROUND
  Vascular endothelial dysfunction in human heart failure contributes to increased tone, exercise limitation, and dysregulation of venous capacitance and vascular volume. The NADPH oxidases (Nox) are an important source of oxidative stress, but their role in the endothelial dysfunction of human heart failure remains unknown.
  
  
  METHODS
  Endothelium-dependent and -independent vasorelaxation were assessed in saphenous vein segments obtained from consecutive patients with heart failure (n = 19) or normal left ventricular function (control; n = 35) undergoing coronary artery bypass graft. Saphenous vein superoxide production was measured by lucigenin-enhanced chemiluminescence and messenger ribonucleic acid expression of relevant transcripts quantified by real-time polymerase chain reaction.
  
  
  RESULTS
  Heart failure patients had significantly worse endothelial function than control subjects (15.2 +/- 3% vs. 40.5 +/- 8.4% relative relaxation; p < 0.05), elevated C-reactive protein (CRP) levels (8.6 +/- 2.7 mg/l vs. 2.6 +/- 0.4 mg/l; p < 0.05), over 2-fold higher NADPH-dependent superoxide generation (p < 0.05), and significantly higher expression of the Nox4 isoform and regulatory subunit p67phox. Superoxide levels were positively correlated with New York Heart Association functional class (r = 0.684; p < 0.05) and CRP (r = 0.501; p < 0.005; n = 32).
  
  
  CONCLUSIONS
  Venous endothelial dysfunction in human heart failure is associated with increased Nox-derived superoxide generation. Inflammatory mechanisms may be involved in the increased reactive oxygen species generation.
authors.affiliation: Cardiovascular Division, King's College London School of Medicine, London, United Kingdom.
authors.forename: Rafał
authors.initials: R
authors.lastname: Dworakowski
authors.forename: Simon
authors.initials: S
authors.lastname: Walker
authors.forename: Aziz
authors.initials: A
authors.lastname: Momin
authors.forename: Jatin
authors.initials: J
authors.lastname: Desai
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Gamel
authors.forename: Olaf
authors.initials: O
authors.lastname: Wendler
authors.forename: Mark T
authors.initials: MT
authors.lastname: Kearney
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D017079:Exercise Tolerance; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism*; D009609:Nitrous Oxide / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012501:Saphenous Vein; D013481:Superoxides / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D013481:Superoxides; D002097:C-Reactive Protein; D019255:NADPH Oxidases; D009609:Nitrous Oxide