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Research Paper

Stent Implantation Activates RhoA in Human Arteries: Inhibitory Effect of Rapamycin

Guérin P.a · Sauzeau V.a · Rolli-Derkinderen M.a · Al Habbash O.b · Scalbert E.c · Crochet D.a · Pacaud P.a · Loirand G.a

Author affiliations

aINSERM U 533, Faculté des Sciences and bDepartment of Cardiac Surgery, CHU, Nantes, and cInstitut de Recherche International Servier, Suresnes, France

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J Vasc Res 2005;42:21–28

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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: May 19, 2004
Accepted: October 05, 2004
Published online: January 28, 2005
Issue release date: January – February

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 0

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

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

Abstract

In-stent restenosis is a novel pathobiologic process resulting from vascular smooth muscle cell (VSMC) proliferation, migration and excessive matrix production. The present study was designed to assess the activity of RhoA, a major regulator of VSMC proliferation and migration, after stenting and to determine its role in the neointimal formation. Analysis of RhoA activity in an ex vivo organ culture model of human internal mammary arteries demonstrates that stenting induced a time-dependent increase in RhoA activity (4.9 ± 0.4 vs. 1.2 ± 0.2 in control at 28 days, n = 4, p < 0.0001) associated with a concomitant decrease in p27 expression. Treatment of stented arteries with the permeant RhoA inhibitor TAT-C3 (10 µg/ml) or Rho-kinase inhibitors (Y-27632, 10 µmol/l; fasudil, 10 µmol/l) inhibited both neointimal formation and decrease in p27 expression. Rapamycin (1 and 10 nmol/l) also inhibited neointimal formation, and induced a loss of RhoA expression. The inhibitory effect of rapamycin on neointimal thickening is prevented by the dominant active form of RhoA. Our study shows that stent implantation induces maintained RhoA activation and demonstrates that the inhibitory action of rapamycin on RhoA expression plays a key role in its antirestenotic effect.

© 2005 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: May 19, 2004
Accepted: October 05, 2004
Published online: January 28, 2005
Issue release date: January – February

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 0

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

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


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