Vascular Effects Following Homozygous Disruption of p47 phox: An Essential Component of NADPH Oxidase
Open accessAbstract
Background —Evidence suggests that the vessel wall contains an oxidase similar, if not identical, to phagocytic NADPH oxidase. We tested the contribution of this specific oxidase to the progression of atherosclerosis and the regulation of blood pressure. Methods and Results —An examination of aortic rings from wild-type mice and mice with homozygous targeted disruptions in p47 phox revealed that p47 phox knockout mice had a reduction in vascular superoxide production. However, analyses of apoE −/− p47 phox +/+ and apoE −/− p47 phox −/− strains of mice demonstrated no significant differences in atherosclerotic lesion sizes. Similarly, analyses of wild-type and p47 phox knockout mice revealed no differences in either basal blood pressure or the rise in blood pressure seen after the pharmacological inhibition of nitric oxide synthase. Conclusions —NADPH oxidase contributes to basal vascular superoxide production. However, the absence of a functional oxidase does not significantly affect the progression of atherosclerosis in the standard mouse apoE −/− model, nor does it significantly influence basal blood pressure.
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In other cases, increased expression of endothelial NOX2 has not been linked to pathological conditions even though increased production of superoxide and macrophage recruitment was observed.
“However, in other cases, an increased expression of endothelial NOX2 has not been linked to pathological conditions even though an increased production of superoxide and macrophage recruitment was observed (243, 443).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [443]
Some reports do not find significant differences in atherosclerosis progression or lesion size with p47phox−/− ApoE−/−.
“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 [443]
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References 23 · Cited by 158
Research works printed but not linked: 2
- DeKeulenaer GW, Alexander RW, Ushio-Fukai M, Ishizaka N, Griendling KK. Tumor necrosis factor alpha activities a p22(phox)-based NADH oxidase in vascular smooth muscle. Biochem J. 1998;329: 653-657.
- Harrison DG, Ohara Y. Physiological consequences of increased vascular oxidant stresses in hypercholesterolemia and atherosclerosis: implications for impaired vasomotion. Am J Cardiol. 1995;75:B75-B81.
- Authors
- Hsich, E., Segal, B. H., Pagano, P. J., Rey, F. E., Paigen, B., Deleonardis, J., Hoyt, R. F., Holland, S. M., & Finkel, T.
- Affiliations
- National Institutes of Health (US)
- Venue
- Circulation
- Published
- 2000-03-21
- Volume
- 101
- Issue
- 11
- Pages
- 1234-1236
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1984486105
- Cited by
- 158
- References
- 23
- Citations by year
- 2025: 3 · 2024: 2 · 2021: 3 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 9 · 2013: 5 · 2012: 11
- FWCI
- 9.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- 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
- p47phox, NADPH oxidase, atherosclerosis, blood pressure regulation, ApoE-deficient mice, nitric oxide synthase inhibition, knockout mice
- MeSH terms
- Animals, Aorta, Apolipoproteins E, Arteriosclerosis, Blood Pressure, Blood Vessels, Enzyme Inhibitors, Homozygote, Mice, Inbred C57BL, Phosphoproteins, Superoxides, Mice, Knockout, Nitric Oxide Synthase, NADPH Oxidases, NG-Nitroarginine Methyl Ester, Mice, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, In Vitro Techniques
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