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Cited by 171Nitric Oxide and Endothelin EffectsAtherosclerosis and Cardiovascular DiseasesNeutrophil, Myeloperoxidase and Oxidative Mechanisms

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.

Impaired Superoxide Production Due to a Deficiency in Phagocyte NADPH Oxidase Fails to Inhibit Atherosclerosis in Mice

Kirk, Elizabeth A., Dinauer, Mary C., Rosen, Henry, Chait, Alan, Heinecke, Jay W., LeBoeuf, Renée C.·2000·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/01.atv.20.6.1529
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Abstract

Abstract—Superoxide, the reduced form of molecular oxygen, has been implicated in the genesis of vascular disease. One potential mechanism involves oxidation of low density lipoprotein into an atherogenic particle. A second involves reaction with nitric oxide to generate peroxynitrite, a highly oxidizing intermediate. A third involves regulation of signal transduction in artery wall cells. One well-characterized pathway for superoxide production resides in macrophages, the cellular hallmark of the early atherosclerotic lesion. Macrophages contain a membrane-bound NADPH oxidase that reduces oxygen to superoxide. In the current studies, we used mice that are deficient in the gp91-phox subunit of the NADPH oxidase–a model of chronic granulomatous disease (CGD)–to explore the role of superoxide in atherosclerotic vascular disease. Wild-type and CGD mice on the C57BL/6 background received a high-fat diet for 20 weeks to induce hypercholesterolemia. At the end of this period, the 2 strains of mice had comparable plasma lipid levels, and their atherosclerotic lesions were similar in size. We also crossed CGD mice with apolipoprotein E–deficient (apoE−/−) mice to generate spontaneously hypercholesterolemic animals that lacked functional NADPH oxidase. After 24 weeks, the CGD-apoE−/− animals had lower plasma cholesterol and triglyceride levels than did the apoE−/− animals, but there was no difference in the extent of atherosclerotic plaque. Our findings suggest that superoxide generated by the NADPH oxidase of phagocytes does not promote atherosclerosis in mice with either diet-induced or genetic forms of hypercholesterolemia.

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Research works printed but not linked: 7

  1. 1998, Atherosclerosis, 141, 1
  2. 10.1161/res.69.5.1934359 · DOI
  3. 1997, Clin Cardiol, 20, 11
  4. 10.1161/atv91.14.5.8172841 · DOI
  5. 10.1161/atvb.17.9.1734 · DOI
  6. 10.1161/atv91.11.3.2029492 · DOI
  7. 10.1161/circ.96.7.2361 · DOI

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Metadata

Authors
Kirk, E. A., Dinauer, M. C., Rosen, H., Chait, A., Heinecke, J. W., & LeBoeuf, R. C.
Affiliations
  • University of Washington (US)
  • From the Departments of Pathobiology and Nutritional Sciences (E.A.K., R.C.L.) and Medicine (E.A.K., H.R., A.C., R.C.L.), University of Washington, Seattle; the Departments of Pediatrics and Medical and Molecular Genetics (M.C.D.), Indiana University Medical Center, Indianapolis; and the Departments of Medicine and Molecular Biology and Pharmacology (J.W.H.), Washington University School of Medicine, St. Louis, Mo.
ORCID
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2000-06
Volume
20
Issue
6
Pages
1529-1535
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/01.atv.20.6.1529
OpenAlex
W2097082675
Cited by
171
References
49
Citations by year
2025: 1 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 11 · 2014: 12 · 2013: 9 · 2012: 8
FWCI
9.48
Type
journal article
Language
en
Open access
closed
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (7r01ag015013-06, 5r01ag012293-05)
  • National Institute on Aging (AG12293, AG 15013)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 02456)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
superoxide, NADPH oxidase, gp91phox, chronic granulomatous disease, atherosclerosis, macrophages, phagocytes, hypercholesterolemia, apolipoprotein E deficiency, high-fat diet, peroxynitrite, nitric oxide, LDL oxidation, serum cholesterol, triglycerides
MeSH terms
Animals, Apolipoproteins E, Arteriosclerosis, Cholesterol, Female, Male, Mice, Inbred C57BL, NADH, NADPH Oxidoreductases, Phagocytes, RNA, Messenger, Sex Characteristics, Superoxides, Triglycerides, Gene Expression, NADPH Oxidases, Mice

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