Document Detail


Novel NAD(P)H oxidase inhibitor suppresses angioplasty-induced superoxide and neointimal hyperplasia of rat carotid artery.
MedLine Citation:
PMID:  12609967     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neointimal proliferation occurring after vascular or endovascular procedures is a major complication leading to end-organ or limb ischemia. In experimental models, balloon injury has been shown to induce NAD(P)H oxidase to produce vascular superoxide anion (O2*-) production, which has been implicated in cell proliferation, but a direct link is still unclear. We postulated that inhibition of arterial NAD(P)H oxidase, resulting in decreased O2*-, would lessen the neointimal hyperplasia caused by balloon injury to the common carotid artery (CCA). Sprague-Dawley rats were implanted with osmotic minipumps containing either vehicle, a cell-permeant peptide that inhibits NAD(P)H oxidase (gp91ds-tat, 10 mg/kg per day), or a scrambled peptide control (scrmb-tat). Two days after pump implantation, the left CCA was injured using an intravascular balloon embolectomy catheter (2F Fogarty). Systolic blood pressure was monitored by tail cuff. Fourteen days after injury, CCAs were harvested and analyzed by digital morphometry. Rats in both groups remained normotensive, with no significant differences in systolic blood pressure. Reactive oxygen species measurements after injury indicated a significant reduction in vascular O2*- in rats infused with gp91ds-tat, and the neointima/media area and thickness ratios were significantly lower in their arteries compared with control. On the contrary, no significant change in overall CCA diameter was observed in any group. Our data indicate that in response to balloon injury of the rat carotid artery, NAD(P)H oxidase activity contributes to neointimal hyperplasia and is involved in vascular cell proliferation and migration during restenosis.
Authors:
Gary M Jacobson; Hector M Dourron; Jianhua Liu; Oscar A Carretero; Daniel J Reddy; Tanja Andrzejewski; Patrick J Pagano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-02-27
Journal Detail:
Title:  Circulation research     Volume:  92     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-04     Completed Date:  2003-04-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  637-43     Citation Subset:  IM    
Affiliation:
Hypertension and Vascular Research Division, Henry Ford Health System, Detroit, Mich, USA.
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MeSH Terms
Descriptor/Qualifier:
Angioplasty / adverse effects*
Animals
Carotid Arteries / drug effects,  metabolism,  pathology*
Carotid Stenosis / drug therapy*,  etiology,  metabolism,  pathology
Enzyme Inhibitors / pharmacology
Glycoproteins / therapeutic use*
Hyperplasia
Male
NADPH Oxidase / antagonists & inhibitors*
Rats
Rats, Sprague-Dawley
Superoxides / metabolism*
Tyrosine / analogs & derivatives*,  analysis
Grant Support
ID/Acronym/Agency:
HL-28982/HL/NHLBI NIH HHS; HL-55425/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Glycoproteins; 0/gp91ds-tat protein, chimeric; 11062-77-4/Superoxides; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; EC 1.6.3.1/NADPH Oxidase
Comments/Corrections
Comment In:
Circ Res. 2003 Apr 4;92(6):583-5   [PMID:  12676809 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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