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Table of Contents
Vol. 41, No. 3, 2004
Issue release date: May – June
Section title: Research Paper
J Vasc Res 2004;41:252–260
(DOI:10.1159/000078646)

α4β1 Integrin (VLA-4) Blockade Attenuates both Early and Late Leukocyte Recruitment and Neointimal Growth following Carotid Injury in Apolipoprotein E (–/–) Mice

Barringhaus K.G.a · Phillips J.W.a · Thatte J.S.b · Sanders J.M.a · Czarnik A.C.a · Bennett D.K.a · Ley K.F.b,c · Sarembock I.J.a,b
aDepartment of Medicine, Cardiovascular Division, bCardiovascular Research Center, cBiomedical Engineering, University of Virginia Health System, Charlottesville, Va., USA

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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: October 15, 2003
Accepted: February 10, 2004
Published online: June 30, 2004
Issue release date: May – June

Number of Print Pages: 9
Number of Figures: 6
Number of Tables: 0

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: http://www.karger.com/JVR

Abstract

Background: The α4β1 integrin (VLA-4) supports rolling and firm adhesion of leukocytes to inflamed tissues via ligation of VCAM-1 or fibronectin expressed on the activated endothelium. We tested the hypothesis that VLA-4 mediates leukocyte recruitment and neointimal growth after arterial injury in the atherosclerosis-prone apolipoprotein E (ApoE)-deficient mouse. Methods: ApoE (–/–) mice fed a Western diet underwent air desiccation injury, and the expression patterns of VLA-4 and VCAM-1 were determined by immunohistochemistry (IHC). To determine the effect of targeted VLA-4 blockade on leukocyte recruitment and neointimal growth, ApoE (–/–) mice received an intraperitoneal injection of a VLA-4 neutralizing monoclonal antibody (PS/2) at the time of injury alone or over a prolonged administration course. Additional mice received an isotype control antibody. Results: IHC demonstrated a marked increase in VLA-4 expression 7 days following injury. Prolonged administration of PS/2 resulted in a 72% reduction (p < 0.02) in neointimal growth 28 days following injury. IHC revealed a marked 95% reduction in neutrophil recruitment at 7 days and a 48% reduction in macrophage recruitment 28 days following injury with prolonged PS/2 administration. Conclusions: Prolonged VLA-4 blockade reduces leukocyte recruitment and neointimal growth following air desiccation injury in ApoE (–/–) mice. These findings demonstrate an important role for VLA-4 in the response to arterial injury.

© 2004 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: October 15, 2003
Accepted: February 10, 2004
Published online: June 30, 2004
Issue release date: May – June

Number of Print Pages: 9
Number of Figures: 6
Number of Tables: 0

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: http://www.karger.com/JVR


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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