Published Online
on July 1, 2002

A more recent version of this article appeared on July 23, 2002

This Article Full Text (PDF) All Versions of this Article: 106/4/479    most recent 01.CIR.0000022846.22923.46v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sansilvestri-Morel, P. Articles by Vanhoutte, P. M. Search for Related Content PubMed Articles by Sansilvestri-Morel, P. Articles by Vanhoutte, P. M. Related Collections Acute myocardial infarction Other Vascular biology

Submitted on February 19, 2002
Revised on May 8, 2002
Accepted on May 9, 2002

Synthesis of Collagen Is Dysregulated in Cultured Fibroblasts Derived From Skin of Subjects With Varicose Veins as It Is in Venous Smooth Muscle Cells

Patricia Sansilvestri-Morel PhD, Alain Rupin PhD, Stéphane Jaisson , Jean-Noël Fabiani MD, Tony J. Verbeuren PhD, and Paul M. Vanhoutte MD, PhD^*

From the Division of Angiology, Servier Research Institute, Suresnes, and the Department of Cardiovascular Surgery, European Hospital Georges Pompidou, Paris (J.-N.F.), France.

^* To whom correspondence should be addressed. E-mail: vanhoutt{at}servier.fr.

Background—The dilatation and tortuosity observed in varicose veins provide evidence for progressive venous wall remodeling associated with abnormalities of smooth muscle cells and extracellular matrix. The present study was designed to examine if the phenotypic modulations observed in the venous smooth muscle cells of patients with varicose veins were also present in their dermal fibroblasts.

Methods and Results—Collagen type I (collagen I), type III (collagen III), and type V (collagen V) were compared in dermal fibroblasts derived from the skin of control subjects and patients with varicose veins. The synthesis of collagen I, the release of its metabolites, and the expression of its mRNA were increased in fibroblasts from patients with varicose veins, whereas the synthesis of collagen III was decreased but not correlated with a decrease in mRNA expression and in metabolite release. Matrix metalloproteinases (MMP1, 2, 7, 8, 9, and 13) and their inhibitors (TIMP1 and 2) were quantified in both cell types; only the production of proMMP2 was increased in cells derived from patients with varicose veins.

Conclusions—These findings suggest that the synthesis of collagen I and III is dysregulated in dermal fibroblasts derived from patients with varicose veins. These results are comparable with those observed in smooth muscle cells derived from varicose veins, thus suggesting a systemic alteration of tissue remodeling in subjects with varicose veins.

Key words: veins • collagen • metalloproteinases • remodeling

This article has been cited by other articles:

				J D Raffetto and R A Khalil Mechanisms of varicose vein formation: valve dysfunction and wall dilation Phlebology, April 1, 2008; 23(2): 85 - 98. [Abstract] [Full Text] [PDF]

				J. J. Bergan, G. W. Schmid-Schonbein, P. D. C. Smith, A. N. Nicolaides, M. R. Boisseau, and B. Eklof Chronic Venous Disease N. Engl. J. Med., August 3, 2006; 355(5): 488 - 498. [Full Text] [PDF]

				G. Ertl and S. Frantz Healing after myocardial infarction Cardiovasc Res, April 1, 2005; 66(1): 22 - 32. [Abstract] [Full Text] [PDF]

				J. Joseph, S. Ranganathan, and J. L. Mehta Low Density Lipoproteins Modulate Collagen Metabolism in Fibroblasts Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2003; 8(2): 161 - 166. [Abstract] [PDF]