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Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis.

Publication ,  Journal Article
Miller, FJ; Gutterman, DD; Rios, CD; Heistad, DD; Davidson, BL
Published in: Circ Res
June 29, 1998

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-.) 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 x min(-1) x mm(-2), 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-. 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-. throughout the wall of WHHL aorta, especially within layers of smooth muscle. This finding was confirmed by demonstrating increased O2-. levels in smooth muscle cells cultured from WHHL aorta. We conclude that elevated O2-. levels in atherosclerotic vessels are not confined to the endothelium but occur throughout the vascular wall, including smooth muscle cells. Reduction in endothelial O2-. levels is not sufficient to improve endothelium-dependent relaxation. Generation of reactive oxygen species within the media may contribute to vasomotor dysfunction in atherosclerosis.

Duke Scholars

Published In

Circ Res

DOI

ISSN

0009-7330

Publication Date

June 29, 1998

Volume

82

Issue

12

Start / End Page

1298 / 1305

Location

United States

Related Subject Headings

  • Vasodilation
  • Superoxides
  • Reactive Oxygen Species
  • Rabbits
  • Oxidative Stress
  • Muscle, Smooth, Vascular
  • Gene Transfer Techniques
  • Cells, Cultured
  • Cardiovascular System & Hematology
  • Arteriosclerosis
 

Citation

APA
Chicago
ICMJE
MLA
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Miller, F. J., Gutterman, D. D., Rios, C. D., Heistad, D. D., & Davidson, B. L. (1998). Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis. Circ Res, 82(12), 1298–1305. https://doi.org/10.1161/01.res.82.12.1298
Miller, F. J., D. D. Gutterman, C. D. Rios, D. D. Heistad, and B. L. Davidson. “Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis.Circ Res 82, no. 12 (June 29, 1998): 1298–1305. https://doi.org/10.1161/01.res.82.12.1298.
Miller FJ, Gutterman DD, Rios CD, Heistad DD, Davidson BL. Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis. Circ Res. 1998 Jun 29;82(12):1298–305.
Miller, F. J., et al. “Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis.Circ Res, vol. 82, no. 12, June 1998, pp. 1298–305. Pubmed, doi:10.1161/01.res.82.12.1298.
Miller FJ, Gutterman DD, Rios CD, Heistad DD, Davidson BL. Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis. Circ Res. 1998 Jun 29;82(12):1298–1305.

Published In

Circ Res

DOI

ISSN

0009-7330

Publication Date

June 29, 1998

Volume

82

Issue

12

Start / End Page

1298 / 1305

Location

United States

Related Subject Headings

  • Vasodilation
  • Superoxides
  • Reactive Oxygen Species
  • Rabbits
  • Oxidative Stress
  • Muscle, Smooth, Vascular
  • Gene Transfer Techniques
  • Cells, Cultured
  • Cardiovascular System & Hematology
  • Arteriosclerosis