| Regression of atherosclerosis in monkeys reduces vascular superoxide levels. | |
| | |
MedLine Citation:
|
PMID: 11861415 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Christopher A Hathaway; Donald D Heistad; Donald J Piegors; Francis J Miller |
Related Documents
:
|
21799125 - Pulmonary hemodynamics and vascular reactivity in asphyxiated term lambs resuscitated w... 18703045 - Decreased plasma and cardiac matrix metalloproteinase activities in patients with coron... 16159605 - Measurement of flow-mediated dilatation of the brachial artery is affected by local ela... 10030385 - Distribution and prevalence of inducible nitric oxide synthase in atherosclerotic vesse... 2876115 - Comparison of vascular responses of isolated, perfused simian and canine coronary arter... 12923335 - Superior orbital rim approach for anterior communicating artery aneurysms: a surgical s... |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Circulation research Volume: 90 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2002 Feb |
Date Detail:
|
Created Date: 2002-02-25 Completed Date: 2002-02-27 Revised Date: 2013-03-05 |
Medline Journal Info:
|
Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
|
Languages: eng Pagination: 277-83 Citation Subset: IM |
Affiliation:
|
Department of Internal Medicine, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetylcholine
/
pharmacology Animals Arteries / drug effects, metabolism, pathology Arteriosclerosis / pathology, physiopathology* Cholesterol / blood Diet, Atherogenic Disease Models, Animal Enzyme Inhibitors / pharmacology Fluorescent Dyes Immunohistochemistry Lipoproteins, LDL / blood Macaca fascicularis Macrophages / pathology Male Membrane Transport Proteins* NADP / pharmacology NADPH Dehydrogenase / metabolism NADPH Oxidase / antagonists & inhibitors, metabolism Phosphoproteins / metabolism Remission, Spontaneous* Superoxides / metabolism* Vasomotor System / drug effects, physiopathology |
| Grant Support | |
ID/Acronym/Agency:
|
HL-03669/HL/NHLBI NIH HHS; HL-14388/HL/NHLBI NIH HHS; HL-16066/HL/NHLBI NIH HHS; HL-37386/HL/NHLBI NIH HHS; HL-62984/HL/NHLBI NIH HHS; K08 HL003669/HL/NHLBI NIH HHS; K08 HL003669-03/HL/NHLBI NIH HHS; K08 HL003669-04/HL/NHLBI NIH HHS; K08 HL003669-05/HL/NHLBI NIH HHS; NS-24621/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Enzyme Inhibitors; 0/Fluorescent Dyes; 0/Lipoproteins, LDL; 0/Membrane Transport Proteins; 0/Phosphoproteins; 11062-77-4/Superoxides; 51-84-3/Acetylcholine; 53-59-8/NADP; 57-88-5/Cholesterol; EC 1.6.3.1/CYBA protein, human; EC 1.6.3.1/NADPH Oxidase; EC 1.6.3.1/neutrophil cytosolic factor 1; EC 1.6.99.1/NADPH Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disea...
Next Document: Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after fo...