p47phox is required for atherosclerotic lesion progression in ApoE–/– mice
Open accessAbstract
NADPH oxidase is upregulated in smooth muscle cells (SMCs) in response to growth factor stimulation, concomitant with increased reactive oxygen species (ROS) production. We investigated the role of ROS production by NADPH oxidase in SMC responses to growth factors and in atherosclerotic lesion formation in ApoE(-/-) mice. SMCs from wild-type, p47phox(-/-), and gp91phox(-/-) mice differed markedly with respect to growth factor responsiveness and ROS generation. p47phox(-/-) SMCs had diminished superoxide production and a decreased proliferative response to growth factors compared with wild-type cells, whereas the response of gp91phox(-/-) SMCs was indistinguishable from that of wild-type SMCs. The relevance of these in vitro observations was tested by measuring atherosclerotic lesion formation in genetically modified (wild-type, p47phox(-/-), ApoE(-/-), and ApoE(-/-)/p47phox(-/-)) mice. ApoE(-/-)/p47phox(-/-) mice had less total lesion area than ApoE(-/-) mice, regardless of whether mice were fed standard chow or a high-fat diet. Together, these studies provide convincing support for the hypothesis that superoxide generation in general, and NADPH oxidase in particular, have a requisite role in atherosclerotic lesion formation, and they provide a rationale for further studies to dissect the contributions of ROS to vascular lesion formation.
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Mice combining the mutation of p47phox−/− with ApoE−/− appear to be protected from atherosclerotic lesions compared with ApoE−/− mice.
“The mice combining the mutation of p47phox−/− with ApoE−/− appear to be protected from atherosclerotic lesions (253) compared with ApoE−/− mice (64, 976), although some reports do not find significant differences in atherosclerosis progression or lesion size (443).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [64]
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- Authors
- Barry-Lane, P. A., Patterson, C., van der Merwe, M., Hu, Z., Holland, S. M., Yeh, E. T. H., & Runge, M. S.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- National Cancer Institute (US)
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- Runge, Marschall S.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-11-15
- Volume
- 108
- Issue
- 10
- Pages
- 1513-1522
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC209414
- OpenAlex
- W2088204476
- Cited by
- 489
- References
- 48
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 14 · 2020: 8 · 2019: 10 · 2018: 16 · 2017: 23 · 2016: 23 · 2015: 23 · 2014: 29 · 2013: 22 · 2012: 27
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r01hl059652-04)
- National Heart, Lung, and Blood Institute (R01HL057352)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- p47phox, NADPH oxidase, atherosclerosis, atherosclerosis progression, ApoE-deficient mice, smooth muscle cells, reactive oxygen species, superoxide production, gp91phox, growth factor responsiveness, cell proliferation, high-fat diet
- MeSH terms
- Animals, Apolipoproteins E, Arteriosclerosis, Base Sequence, Cell Division, Mice, Inbred C57BL, Muscle, Smooth, Vascular, Phosphoproteins, Reactive Oxygen Species, DNA Primers, Disease Progression, NADPH Oxidases, Mice
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