| Paclitaxel impairs endothelial cell adhesion but not cytokine-induced cellular adhesion molecule expression. | |
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MedLine Citation:
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PMID: 15834684 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Local delivery of antiproliferative agents using drug-eluting stents has become a productive area of research for preventing in-stent restenosis. Recently, the microtubule stabilizing drug paclitaxel has been used to coat stents. While the actions of paclitaxel on smooth muscle are well documented, effects on endothelial cells (ECs) are largely unknown. Nevertheless, restoration of EC function is a critical step in repairing the vascular lesion. We assessed the effects of paclitaxel by examining three events that are critical in controlling the severity of vascular injury: (1) adhesion of ECs to matrix proteins, (2) EC migration, and (3) cytokine-stimulated cellular adhesion molecule (CAM) expression on the surface of ECs. Paclitaxel inhibited both EC adhesion and migration of ECs; however, it had no effect on tumor necrosis-stimulated CAM expression on ECs. The mechanisms of paclitaxel action on matrix adhesion and migration are not clear, but protein kinase C and myosin light chain kinase do not appear to play a role as they are unaffected by treatment of the cells with paclitaxel. On the other hand, the MAP kinase ERK1/2 is modestly inhibited by paclitaxel. While paclitaxel-coated endovascular stents may prevent smooth muscle proliferation, their attenuation of EC migration and adhesion to the lesion coupled with an inability to reduce cytokine-induced CAM expression on ECs may limit their effectiveness. |
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Authors:
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Harold W Davis; Elizabeth VandenBerg; Maria D Reid; Prabir Roy-Chaudhury; John D Edwards |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Annals of vascular surgery Volume: 19 ISSN: 0890-5096 ISO Abbreviation: Ann Vasc Surg Publication Date: 2005 May |
Date Detail:
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Created Date: 2005-05-25 Completed Date: 2005-08-15 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8703941 Medline TA: Ann Vasc Surg Country: United States |
Other Details:
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Languages: eng Pagination: 398-406 Citation Subset: IM |
Affiliation:
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Division of Vascular Surgery, University of Cincinnati Medical Center, Cincinnati, OH 45267-0558, USA. harold.davis@uc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology Antineoplastic Agents, Phytogenic / pharmacology* Cell Adhesion / drug effects* Cell Movement / drug effects Endothelial Cells / drug effects*, physiology Humans Myosin-Light-Chain Kinase / physiology Nocodazole / pharmacology Paclitaxel / pharmacology* Phosphorylation Protein Kinase C / physiology Protein Kinases / physiology |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Antineoplastic Agents, Phytogenic; 31430-18-9/Nocodazole; 33069-62-4/Paclitaxel; EC 2.7.-/Protein Kinases; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.18/Myosin-Light-Chain Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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