title: Calcium-dependent NOX5 nicotinamide adenine dinucleotide phosphate oxidase contributes to vascular oxidative stress in human coronary artery disease.
abstract: OBJECTIVE
  This study sought to examine the expression and activity of the calcium-dependent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in human atherosclerotic coronary arteries.
  
  
  BACKGROUND
  The NOX-based NADPH oxidases are major sources of reactive oxygen species (ROS) in human vessels. Several NOX homologues have been identified, but their relative contribution to vascular ROS production in coronary artery disease (CAD) is unclear; NOX5 is a unique homolog in that it is calcium dependent and thus could be activated by vasoconstrictor hormones. Its presence has not yet been studied in human vessels.
  
  
  METHODS
  Coronary arteries from patients undergoing cardiac transplantation with CAD or without CAD were studied; NOX5 was quantified and visualized using Western blotting, immunofluorescence, and quantitative real-time polymerase chain reaction. Calcium-dependent NADPH oxidase activity, corresponding greatly to NOX5 activity, was measured by electron paramagnetic resonance.
  
  
  RESULTS
  Both Western blotting and quantitative real-time polymerase chain reaction indicated a marked increase in NOX5 protein and messenger ribonucleic acid (mRNA) in CAD versus non-CAD vessels. Calcium-dependent NADPH-driven production of ROS in vascular membranes, reflecting NOX5 activity, was increased 7-fold in CAD and correlated significantly with NOX5 mRNA levels among subjects. Immunofluorescence showed that NOX5 was expressed in the endothelium in the early lesions and in vascular smooth muscle cells in the advanced coronary lesions.
  
  
  CONCLUSIONS
  These studies identify NOX5 as a novel, calcium-dependent source of ROS in atherosclerosis.
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Guzik
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Maria C
authors.initials: MC
authors.lastname: Gongora
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Guzik
authors.forename: Heinrich E
authors.initials: HE
authors.lastname: Lob
authors.forename: Deepa
authors.initials: D
authors.lastname: Mangalat
authors.forename: Nyssa
authors.initials: N
authors.lastname: Hoch
authors.forename: Sergey
authors.initials: S
authors.lastname: Dikalov
authors.forename: Pawel
authors.initials: P
authors.lastname: Rudzinski
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Kapelak
authors.forename: Jerzy
authors.initials: J
authors.lastname: Sadowski
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000201:enzymology*; D003331:Coronary Vessels / Q000201:enzymology; D004727:Endothelium / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D010865:Pilot Projects; D012333:RNA, Messenger; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases; C431571:NOX5 protein, human; D002118:Calcium