Document Detail


Effects of an alpha-4 integrin inhibitor on restenosis in a new porcine model combining endothelial denudation and stent placement.
MedLine Citation:
PMID:  21179441     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Restenosis remains the main complication of balloon angioplasty and/or stent implantation. Preclinical testing of new pharmacologic agents preventing restenosis largely rely on porcine models, where restenosis is assessed after endothelial abrasion of the arterial wall or stent implantation. We combined endothelial cell denudation and implantation of stents to develop a new clinically relevant porcine model of restenosis, and used this model to determine the effects of an α4 integrin inhibitor, ELN 457946, on restenosis. Balloon-angioplasty endothelial cell denudation and subsequent implantation of bare metal stents in the left anterior descending coronary, iliac, and left common carotid arteries was performed in domestic pigs, treated with vehicle or ELN 457946, once weekly via subcutaneous injections, for four weeks. After 1 month, histopathology and morphometric analyses of the arteries showed complete healing and robust, consistent restenotic response in stented arteries. Treatment with ELN 457946 resulted in a reduction in the neointimal response, with decreases in area percent stenosis between 12% in coronary arteries and 30% in peripheral vessels. This is the first description of a successful pig model combining endothelial cell denudation and bare metal stent implantation. This new double injury model may prove particularly useful to assess pharmacological effects of drug candidates on restenosis, in coronary and/or peripheral arteries. Furthermore, the ELN 457946 α4 integrin inhibitor, administered subcutaneously, reduced inflammation and restenosis in stented coronary and peripheral arteries in pigs, therefore representing a promising systemic therapeutic approach in reducing restenosis in patients undergoing angioplasty and/or stent implantation.
Authors:
Anne Braun; Lilibeth Dofiles; Serge Rousselle; Luis Guerrero; Jane Gunther; Ted Yednock; Alain Stricker-Krongrad; Elizabeth Messersmith
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-13
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-12-23     Completed Date:  2011-07-05     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e14314     Citation Subset:  IM    
Affiliation:
Charles River Laboratories, Preclinical Services Massachusetts, Shrewsbury, Massachusetts, United States of America. bostonegles@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Angioplasty, Balloon, Coronary / methods*
Animals
Coronary Restenosis
Disease Models, Animal
Drug Design
Endothelial Cells / cytology*
Inflammation
Integrin alpha4 / chemistry*,  metabolism
Male
Stents
Swine
Treatment Outcome
Tunica Intima / pathology
Chemical
Reg. No./Substance:
143198-26-9/Integrin alpha4
Comments/Corrections

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


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