Journal article
Superoxide Production in Vascular Smooth Muscle Contributes to Oxidative Stress and Impaired Relaxation in Atherosclerosis
Circulation research, Vol.82(12), pp.1298-1305
06/29/1998
DOI: 10.1161/01.RES.82.12.1298
PMID: 9648726
Abstract
The endothelium is a source of reactive oxygen species in short-term models of hypercholesterolemia and atherosclerosis. We examined a chronic model of atherosclerosis for increased vascular production of superoxide (O2 [center dot]) and determined whether endothelial overexpression of superoxide dismutase (SOD) would improve endothelium-dependent relaxation. Superoxide generation was 3 times higher in isolated aortas from Watanabe heritable hyperlipidemic (WHHL) rabbits (2 to 4 years old) compared with aortas from New Zealand White (NZ) rabbits (43 +/- 10 versus 14 +/- 2 relative light units [center dot] min [center dot] mm, n=9, P<0.05). After in vitro transduction with adenovirus containing the gene for CuZn-SOD (AdCMVCuZn-SOD) or extracellular SOD (AdCMVEC-SOD), endothelial O2 [center dot] levels in WHHL aortas were significantly reduced. Gene transfer of SOD to WHHL aortas, however, failed to improve the impaired relaxation to acetylcholine or calcium ionophore. By use of the oxidative fluorescent dye hydroethidine, an in situ assay indicated markedly increased generation of O2 [center dot] throughout the wall of WHHL aorta, especially within layers of smooth muscle. This finding was confirmed by demonstrating increased O2 [center dot] levels in smooth muscle cells cultured from WHHL aorta. We conclude that elevated O2 [center dot] levels in atherosclerotic vessels are not confined to the endothelium but occur throughout the vascular wall, including smooth muscle cells. Reduction in endothelial O2 [center dot] levels is not sufficient to improve endothelium-dependent relaxation. Generation of reactive oxygen species within the media may contribute to vasomotor dysfunction in atherosclerosis. (Circ Res. 1998;82:1298-1305.)
Details
- Title: Subtitle
- Superoxide Production in Vascular Smooth Muscle Contributes to Oxidative Stress and Impaired Relaxation in Atherosclerosis
- Creators
- Francis J Miller - Received September 17, 1997; accepted March 24, 1998. From the Department of Internal Medicine, University of Iowa College of Medicine and Cardiovascular Center, and Veterans Administration Medical Center, Iowa City, Iowa. Correspondence to Francis J. Miller, Jr, MD, E315 General Hospital, Department of Internal Medicine, University of Iowa Hospitals, Iowa City, IA 52242. E-mail francis-miller@uiowa.eduDavid D GuttermanC. David RiosDonald D HeistadBeverly L Davidson
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.82(12), pp.1298-1305
- Publisher
- American Heart Association, Inc
- DOI
- 10.1161/01.RES.82.12.1298
- PMID
- 9648726
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 06/29/1998
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040554402771
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