Document Detail


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
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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:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  277-83     Citation Subset:  IM    
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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; 53-59-8/NADP; 97C5T2UQ7J/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; N9YNS0M02X/Acetylcholine

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