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Research Paper

Identification of Differentially Expressed Genes in Human Varicose Veins: Involvement of Matrix Gla Protein in Extracellular Matrix Remodeling

Cario-Toumaniantz C.a, b · Boularan C.a, b · Schurgers L.J.g · Heymann M.-F.c · Le Cunff M.a, d · Léger J.a, d, e · Loirand G.a, b, f · Pacaud P.a, b

Author affiliations

aINSERM, U533, bUniversité de Nantes, Faculté des Sciences et Techniques, l’Institut du Thorax, cCHU Nantes, Service d’anatomo-pathologie, Hôpital Guillaume et René Laënnec, dUniversité de Nantes, Faculté de médecine, l’Institut du Thorax, eOuest-Genopôle, fCHU Nantes, l’Institut du Thorax, Nantes, France; gDepartment of Biochemistry, University of Maastricht, Maastricht, The Netherlands

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J Vasc Res 2007;44:444–459

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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: May 02, 2007
Accepted: May 07, 2007
Published online: July 20, 2007
Issue release date: October 2007

Number of Print Pages: 16
Number of Figures: 6
Number of Tables: 2

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

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

Abstract

This study was designed to identify the global pattern of differentially expressed genes in human varicose veins. Using suppressive subtractive hybridization, we identified overexpression of genes known to be associated with extracellular matrix remodeling, including collagen III, tissue inhibitor of metalloproteinases I, dermatopontin, matrix Gla protein (MGP) and tenascin C. Real-time polymerase chain reaction analysis confirmed the differential expression of these genes. The overexpression of MGP transcript was associated with increased MGP level in varicose veins, in particular the undercarboxylated form of the protein. Smooth muscle cells from varicose veins showed increased proliferation rate and enhanced matrix mineralization. This observation correlated with the presence of ectopic mineralization areas in the varicose vein walls. The use of warfarin, to inhibit MGP activity, or siRNA targeting MGP transcript induced a reduction in the exacerbated proliferation of varicose vein smooth muscle cells. Our results suggest that high expression of MGP in varicose veins may contribute to venous wall remodeling by affecting proliferation and mineralization processes probably through impaired carboxylation of MGP. In addition, suppressive subtractive hybridization results also produce a profile of differentially expressed genes in varicose veins, in particular extracellular matrix components. Further study of these genes will provide insights into their specific roles in the etiology of venous disease.

© 2007 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: May 02, 2007
Accepted: May 07, 2007
Published online: July 20, 2007
Issue release date: October 2007

Number of Print Pages: 16
Number of Figures: 6
Number of Tables: 2

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

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


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