Cited by 847Nitric Oxide and Endothelin EffectsNeutrophil, Myeloperoxidase and Oxidative MechanismsAtherosclerosis and Cardiovascular Diseases

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. +4 more·2002·Circulation

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 α-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 α-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.

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Crossref · 10.1161/01.cir.0000012917.74432.66

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Authors
Sorescu, D., Weiss, D., Lassègue, B., Clempus, R. E., Szöcs, K., Sorescu, G. P., Valppu, L., Quinn, M. T., Lambeth, J. D., Vega, J. D., Taylor, W. R., & Griendling, K. K.
Affiliations
  • Emory University (US)
  • From the Department of Medicine (D.S., D.W., B.L., R.E.C., K.S., G.P.S., L.V., W.R.T., K.K.G.), Division of Cardiology, Department of Pathology and Laboratory Medicine (J.D.L.), and Department of Surgery (J.D.V.), Emory University, Atlanta, Ga, and the Department of Veterinary Molecular Biology (M.T.Q.), Montana State University, Bozeman, Mont.
Venue
Circulation
Published
2002-03-26
Volume
105
Issue
12
Pages
1429-1435
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
OpenAlex
W2102202839
Cited by
847
References
23
Citations by year
2026: 7 · 2025: 18 · 2024: 13 · 2023: 23 · 2022: 12 · 2021: 19 · 2020: 21 · 2019: 20 · 2018: 18 · 2017: 32 · 2016: 37 · 2015: 36 · 2014: 37 · 2013: 46 · 2012: 56
FWCI
33.97
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
superoxide production, NADPH oxidase, gp91phox, p22phox, NOX4, NOX1, coronary artery disease, plaque macrophages, oxidative stress, plaque shoulder, human coronary arteries
MeSH terms
NADPH Oxidase 2, NADPH Oxidase 4, Arteriosclerosis, Cells, Cultured, Coronary Artery Disease, Coronary Vessels, Endothelium, Vascular, Female, Fibroblasts, Fluorescent Antibody Technique, Fluorescent Dyes, Heart Failure, Humans, Isoenzymes, Male, Membrane Glycoproteins, Middle Aged, Muscle, Smooth, Vascular, NADH, NADPH Oxidoreductases, NADPH Dehydrogenase, Phosphoproteins, RNA, Messenger, Superoxides, Polymerase Chain Reaction, NADPH Oxidases, Membrane Transport Proteins

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