Journal article
Regression of atherosclerosis in monkeys reduces vascular superoxide levels
Circulation research, Vol.90(3), pp.277-283
2002
DOI: 10.1161/hh0302.104724
PMID: 11861415
Abstract
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.
Details
- Title: Subtitle
- Regression of atherosclerosis in monkeys reduces vascular superoxide levels
- Creators
- Christopher A HATHAWAY - Department of Internal Medicine, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa, United StatesDonald D HEISTAD - Department of Internal Medicine, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa, United StatesDonald J PIEGORS - Department of Internal Medicine, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa, United StatesFrancis J MILLER - Department of Internal Medicine, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.90(3), pp.277-283
- Publisher
- Lippincott; Hagerstown, MD
- DOI
- 10.1161/hh0302.104724
- PMID
- 11861415
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 2002
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040204202771
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