Document Detail

Resveratrol inhibits neointimal formation after arterial injury through an endothelial nitric oxide synthase-dependent mechanism.
MedLine Citation:
PMID:  22552115     Owner:  NLM     Status:  MEDLINE    
Revascularization procedures used for treatment of atherosclerosis often result in restenosis. Resveratrol (RSV), an antioxidant with cardiovascular benefits, decreases neointimal formation after arterial injury by a mechanism that is still not fully clarified. Our main objective was to address the role of nitric oxide synthases (NOSes) and more specifically the endothelial-NOS (eNOS) isoform as a mediator of this effect. RSV (4 mg/kg/day, s.c.) alone or in combination with the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) (2 mg/kg/day, s.c.) was given to Sprague-Dawley rats beginning at 3 days before arterial (carotid or aortic) injury. RSV reduced neointimal formation by 50% (P<0.01), decreased intimal cell proliferation by 37% (P<0.01) and reduced inflammatory markers such as PECAM and MMP-9 mRNA. These effects of RSV were all abolished by coadministration of l-NAME. Oral RSV (beginning at 5 days before arterial injury) reduced neointimal thickness after femoral wire injury in mice, however this effect was not observed in eNOS knockout mice. This is the first report of RSV decreasing neointimal cell proliferation and neointimal growth through an eNOS-dependent mechanism.
Danna M Breen; Vernon W Dolinsky; Hangjun Zhang; Husam Ghanim; June Guo; Margaret Mroziewicz; Evangelia L Tsiani; Michelle P Bendeck; Paresh Dandona; Jason R B Dyck; Scott P Heximer; Adria Giacca
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-27
Journal Detail:
Title:  Atherosclerosis     Volume:  222     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-28     Completed Date:  2012-09-20     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  375-81     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada.
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MeSH Terms
Administration, Oral
Antigens, CD31 / genetics
Aorta / drug effects*,  enzymology,  injuries,  pathology
Cardiovascular Agents / administration & dosage,  pharmacology*
Carotid Arteries / drug effects*,  enzymology,  pathology
Carotid Artery Injuries / drug therapy*,  enzymology,  genetics,  pathology
Cell Proliferation / drug effects
Disease Models, Animal
Enzyme Inhibitors / pharmacology
Femoral Artery / drug effects*,  enzymology,  injuries,  pathology
Gene Expression Regulation
Matrix Metalloproteinase 9 / genetics
Mice, Inbred C57BL
Mice, Knockout
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase Type III / antagonists & inhibitors,  deficiency,  genetics,  metabolism*
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Stilbenes / administration & dosage,  pharmacology*
Time Factors
Vascular System Injuries / drug therapy*,  enzymology,  genetics,  pathology
Reg. No./Substance:
0/Antigens, CD31; 0/Cardiovascular Agents; 0/Enzyme Inhibitors; 0/RNA, Messenger; 0/Stilbenes; 50903-99-6/NG-Nitroarginine Methyl Ester; EC Oxide Synthase Type III; EC protein, mouse; EC protein, rat; EC 3.4.24.-/Mmp9 protein, rat; EC Metalloproteinase 9; Q369O8926L/resveratrol

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