| Flow-induced neointimal regression in baboon polytetrafluoroethylene grafts is associated with decreased cell proliferation and increased apoptosis. | |
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MedLine Citation:
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PMID: 12469058 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: We have previously shown that baboon grafts subjected to elevated shear stress exhibit an increase in luminal area through atrophy of the neointimal layer. This study was designed to investigate the smooth muscle cell (SMC) growth kinetics during early regression and evaluate the influence of nitric oxide (NO) in the regulation of this process. METHODS: Sixteen baboons underwent bilateral polytetrafluorethylene aortoiliac graft placement. After development of a neointima over an 8-week period, blood flow through one graft was increased with placement of a downstream arteriovenous fistula. Grafts were harvested at 4 (n = 6), 7 (n = 5), and 14 (n = 5) days and assessed for neointimal cross-sectional area, SMC proliferation and apoptosis, and macrophage infiltration. High-flow grafts were compared with contralateral normal-flow controls. Eleven baboons underwent an identical experimental preparation to evaluate the effect of NO inhibition. Eight weeks after graft implantation, the animals were treated with an initial bolus (100 mg/kg) followed by continuous infusion (60 mg/kg/d) of either N(G)-nitro-L-arginine methyl ester (L-NAME; n = 6) or the inactive stereoisomer N(G)-nitro-D-arginine methyl ester (n = 5). Grafts were harvested at 7 days and evaluated with the experimental endpoints detailed previously. RESULTS: Distal fistula placement resulted in a 3.8-fold increase in mean centerline velocity and wall shear stress. Grafts harvested during the initial 14 days after flow manipulation showed a progressive reduction in neointimal cross-sectional area. This change was associated with a decrease in subendothelial SMC proliferation and an increase in neointimal SMC apoptosis, the latter being in the region adjacent to the graft. Animals treated with L-NAME showed a 20% reduction in platelet cyclic guanosine monophosphate and a 17% reduction in serum nitrate/nitrite concentrations. Despite this inhibition of NO production, no effect on the flow-dependent changes in neointimal area, cell proliferation, or apoptosis was observed in the L-NAME-treated baboons. CONCLUSION: The local hemodynamic environment within healing prosthetic grafts modulates neointimal SMC proliferation and apoptosis. An increase in graft flow leads to atrophy of the neointima. |
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Authors:
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Scott A Berceli; Mark G Davies; Richard D Kenagy; Alexander W Clowes |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter Volume: 36 ISSN: 0741-5214 ISO Abbreviation: J. Vasc. Surg. Publication Date: 2002 Dec |
Date Detail:
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Created Date: 2002-12-06 Completed Date: 2003-01-07 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8407742 Medline TA: J Vasc Surg Country: United States |
Other Details:
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Languages: eng Pagination: 1248-55 Citation Subset: IM |
Affiliation:
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Division of Vascular Surgery, University of Florida, FL, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects*, physiology* Blood Vessel Prosthesis / adverse effects* Blood Vessel Prosthesis Implantation* Cell Division / drug effects*, physiology* Disease Models, Animal Male Myocytes, Smooth Muscle / drug effects, physiology Nitric Oxide / analysis, pharmacology Papio Polytetrafluoroethylene / adverse effects* Regional Blood Flow / drug effects*, physiology* Time Factors Tunica Intima / drug effects*, physiopathology* Vascular Diseases / physiopathology*, surgery* |
| Grant Support | |
ID/Acronym/Agency:
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HL 07828/HL/NHLBI NIH HHS; HL 30946/HL/NHLBI NIH HHS; RR 00166/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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10102-43-9/Nitric Oxide; 9002-84-0/Polytetrafluoroethylene |
| Comments/Corrections | |
Erratum In:
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J Vasc Surg. 2004 Dec;40(6):1233 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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