Superoxide production and expression of nox family proteins in human atherosclerosis
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Superoxide production and expression of nox family proteins in human atherosclerosis. / Sorescu, Dan; Weiss, Daiana; Lassègue, Bernard; Clempus, Roza E; Szöcs, Katalin; Sorescu, George P; Valppu, Liisa; Quinn, Mark T; Lambeth, J David; Vega, J David; Taylor, W Robert; Griendling, Kathy K.
in: CIRCULATION, Jahrgang 105, Nr. 12, 26.03.2002, S. 1429-1435.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Superoxide production and expression of nox family proteins in human atherosclerosis
AU - Sorescu, Dan
AU - Weiss, Daiana
AU - Lassègue, Bernard
AU - Clempus, Roza E
AU - Szöcs, Katalin
AU - Sorescu, George P
AU - Valppu, Liisa
AU - Quinn, Mark T
AU - Lambeth, J David
AU - Vega, J David
AU - Taylor, W Robert
AU - Griendling, Kathy K
PY - 2002/3/26
Y1 - 2002/3/26
N2 - 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.METHODS AND 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.
AB - 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.METHODS AND 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.
KW - Arteriosclerosis/metabolism
KW - Cells, Cultured
KW - Coronary Artery Disease/metabolism
KW - Coronary Vessels/chemistry
KW - Endothelium, Vascular/cytology
KW - Female
KW - Fibroblasts/cytology
KW - Fluorescent Antibody Technique
KW - Fluorescent Dyes
KW - Heart Failure/metabolism
KW - Humans
KW - Isoenzymes/genetics
KW - Male
KW - Membrane Glycoproteins/genetics
KW - Membrane Transport Proteins
KW - Middle Aged
KW - Muscle, Smooth, Vascular/cytology
KW - NADH, NADPH Oxidoreductases/biosynthesis
KW - NADPH Dehydrogenase/genetics
KW - NADPH Oxidase 2
KW - NADPH Oxidase 4
KW - NADPH Oxidases/genetics
KW - Phosphoproteins/genetics
KW - Polymerase Chain Reaction
KW - RNA, Messenger/biosynthesis
KW - Superoxides/analysis
U2 - 10.1161/01.cir.0000012917.74432.66
DO - 10.1161/01.cir.0000012917.74432.66
M3 - SCORING: Journal article
C2 - 11914250
VL - 105
SP - 1429
EP - 1435
JO - CIRCULATION
JF - CIRCULATION
SN - 0009-7322
IS - 12
ER -