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. 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.
journal_name
Circulationjournal_title
Circulationauthors
Sorescu D,Weiss D,Lassègue B,Clempus RE,Szöcs K,Sorescu GP,Valppu L,Quinn MT,Lambeth JD,Vega JD,Taylor WR,Griendling KKdoi
10.1161/01.cir.0000012917.74432.66subject
Has Abstractpub_date
2002-03-26 00:00:00pages
1429-35issue
12eissn
0009-7322issn
1524-4539journal_volume
105pub_type
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