title: Superoxide production and expression of nox family proteins in human atherosclerosis.
abstract: BACKGROUND
  NAD(P)H oxidases are important sources of superoxide in the vasculature, the activity of which is associated with risk factors for human atherosclerosis. This study was designed to investigate the localization of superoxide production and the expression of the Nox family of NAD(P)H oxidase proteins (gp91phox, Nox1, and Nox4) in nonatherosclerotic and atherosclerotic human coronary arteries.
  
  
  RESULTS
  In coronary artery segments from explanted human hearts, we examined intracellular superoxide production with dihydroethidium. In nonatherosclerotic coronary arteries, superoxide was present homogenously throughout the intima, media, and adventitia. In atherosclerotic arteries, there was an additional intense area of superoxide in the plaque shoulder, which is rich in macrophages and alpha-actin-positive cells. p22phox colocalized with gp91phox mainly in macrophages, whereas Nox4 was found only in nonphagocytic vascular cells. Expression of gp91phox and p22phox mRNA was associated with the severity of atherosclerosis. gp91phox correlated with the plaque macrophage content, whereas Nox4 correlated with the content of alpha-actin-positive cells. Nox1 expression was low both in human coronary arteries and isolated vascular cells.
  
  
  CONCLUSIONS
  Several Nox proteins, including gp91phox and Nox4, may contribute to increased intracellular oxidative stress in human coronary atherosclerosis in a cell-specific manner and thus may be involved in the genesis and progression of human coronary atherosclerotic disease.
authors.affiliation: Department of Medicine, Emory University, Atlanta, Ga 30322, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Sorescu
authors.forename: Daiana
authors.initials: D
authors.lastname: Weiss
authors.forename: Bernard
authors.initials: B
authors.lastname: Lassègue
authors.forename: Roza E
authors.initials: RE
authors.lastname: Clempus
authors.forename: Katalin
authors.initials: K
authors.lastname: Szöcs
authors.forename: George P
authors.initials: GP
authors.lastname: Sorescu
authors.forename: Liisa
authors.initials: L
authors.lastname: Valppu
authors.forename: Mark T
authors.initials: MT
authors.lastname: Quinn
authors.forename: J David
authors.initials: JD
authors.lastname: Lambeth
authors.forename: J David
authors.initials: JD
authors.lastname: Vega
authors.forename: W Robert
authors.initials: WR
authors.lastname: Taylor
authors.forename: Kathy K
authors.initials: KK
authors.lastname: Griendling
mesh_terms: D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D003331:Coronary Vessels / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D009252:NADPH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase