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Regression of atherosclerosis in monkeys reduces vascular superoxide levels.

Publication ,  Journal Article
Hathaway, CA; Heistad, DD; Piegors, DJ; Miller, FJ
Published in: Circ Res
February 22, 2002

Superoxide (O2*-) in arteries may contribute to atherosclerosis in part by inactivation of nitric oxide. We hypothesized that regression of atherosclerosis in nonhuman primates is associated with a decrease in vascular NAD(P)H oxidase, decreased O2*- levels, and improved endothelium-dependent relaxation. Cynomolgus monkeys (n=28) were fed an atherogenic diet for 47+/-10 (mean+/-SE) months. In carotid arteries (containing advanced lesions), femoral arteries (moderate lesions), and saphena arteries (minimal lesions), we examined O2*- levels and vasomotor function. Compared with vessels from normal monkeys (n=8), O2*- levels (measured by lucigenin-enhanced chemiluminescence) were 3.3-fold higher in carotid, 1.7-fold higher in femoral, and not different in saphena arteries from atherosclerotic monkeys. Dihydroethidium staining also demonstrated increased O2*- levels throughout the vessel wall in femoral and carotid arteries from atherosclerotic monkeys. Components of the NAD(P)H oxidase (p22(phox) and p47(phox)) were increased in atherosclerotic arteries, and immunohistochemistry demonstrated colocalization primarily to areas of macrophage infiltration. Relaxation to acetylcholine was impaired in carotid and femoral, but not saphena, arteries from atherosclerotic monkeys. After 8 months of regression diet (n=9), serum cholesterol decreased to normal, and O2*- levels (basal and NAD(P)H-stimulated), as well as expression of NAD(P)H oxidase, returned toward normal. Relaxation to acetylcholine improved in femoral arteries, but not in the more diseased carotid arteries. We conclude that, in a primate model of moderately severe atherosclerosis and regression of atherosclerosis, changes in endothelial function are inversely related to O2*- and NAD(P)H oxidase levels. Reduction in vascular O2*- during regression of atherosclerosis may contribute to improvement in vasomotor function.

Duke Scholars

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

February 22, 2002

Volume

90

Issue

3

Start / End Page

277 / 283

Location

United States

Related Subject Headings

  • Vasomotor System
  • Superoxides
  • Remission, Spontaneous
  • Phosphoproteins
  • NADPH Oxidases
  • NADPH Dehydrogenase
  • NADP
  • Membrane Transport Proteins
  • Male
  • Macrophages
 

Citation

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Hathaway, C. A., Heistad, D. D., Piegors, D. J., & Miller, F. J. (2002). Regression of atherosclerosis in monkeys reduces vascular superoxide levels. Circ Res, 90(3), 277–283. https://doi.org/10.1161/hh0302.104724
Hathaway, Christopher A., Donald D. Heistad, Donald J. Piegors, and Francis J. Miller. “Regression of atherosclerosis in monkeys reduces vascular superoxide levels.Circ Res 90, no. 3 (February 22, 2002): 277–83. https://doi.org/10.1161/hh0302.104724.
Hathaway CA, Heistad DD, Piegors DJ, Miller FJ. Regression of atherosclerosis in monkeys reduces vascular superoxide levels. Circ Res. 2002 Feb 22;90(3):277–83.
Hathaway, Christopher A., et al. “Regression of atherosclerosis in monkeys reduces vascular superoxide levels.Circ Res, vol. 90, no. 3, Feb. 2002, pp. 277–83. Pubmed, doi:10.1161/hh0302.104724.
Hathaway CA, Heistad DD, Piegors DJ, Miller FJ. Regression of atherosclerosis in monkeys reduces vascular superoxide levels. Circ Res. 2002 Feb 22;90(3):277–283.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

February 22, 2002

Volume

90

Issue

3

Start / End Page

277 / 283

Location

United States

Related Subject Headings

  • Vasomotor System
  • Superoxides
  • Remission, Spontaneous
  • Phosphoproteins
  • NADPH Oxidases
  • NADPH Dehydrogenase
  • NADP
  • Membrane Transport Proteins
  • Male
  • Macrophages