(Circulation. 2000;101:1234.)
© 2000 American Heart Association, Inc.
Brief Rapid Communications |
Vascular Effects Following Homozygous Disruption of p47phox
An Essential Component of NADPH Oxidase
From the Laboratory of Molecular Biology (E.H., T.F.) and the Laboratory of Animal Medicine and Surgery (J.D., R.F.H.), National Heart, Lung, and Blood Institute, and the Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases (B.H.S., S.M.H.), National Institutes of Health, Bethesda, Md; The Jackson Laboratory, Bar Harbor, Maine (B.P.); and the Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich (P.J.P, F.E.R).
Correspondence to Toren Finkel, MD, PhD, National Institutes of Health, Bldg 10-6N/240, 10 Center Drive, Bethesda, MD 20892. E-mail finkelt{at}nih.gov
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 p47phox revealed that p47phox knockout mice had a reduction in vascular superoxide production. However, analyses of apoE -/- p47phox+/+ and apoE -/- p47phox -/- strains of mice demonstrated no significant differences in atherosclerotic lesion sizes. Similarly, analyses of wild-type and p47phox 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.
Key Words: apolipoproteins • atherosclerosis • blood pressure
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