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

• Published in: Circulation (New York, N.Y.) Vol. 106; no. 4; pp. 479 - 483
• Main Authors: Sansilvestri-Morel, Patricia, Rupin, Alain, Jaisson, Stéphane, Fabiani, Jean-Noël, Verbeuren, Tony J., Vanhoutte, Paul M.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 23.07.2002
• Subjects: Aged; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Division; Cells, Cultured; Collagen Type I - biosynthesis; Collagen Type I - genetics; Collagen Type I - metabolism; Collagen Type III - biosynthesis; Collagen Type III - genetics; Collagen Type III - metabolism; Culture Media - analysis; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Fibrillar Collagens - biosynthesis; Fibroblasts - metabolism; Gene Expression Regulation; Humans; Kinetics; Male; Matrix Metalloproteinases - biosynthesis; Medical sciences; Middle Aged; Muscle, Smooth, Vascular - metabolism; Protein Biosynthesis; RNA, Messenger - biosynthesis; Skin - cytology; Skin - metabolism; Tissue Inhibitor of Metalloproteinases - biosynthesis; Varicose Veins - genetics; Varicose Veins - metabolism; Varicose Veins - pathology; Veins - cytology; Veins - metabolism; Human; Enzyme; Pathogenesis; Cardiovascular disease; Metalloendopeptidases; Smooth muscle; Venous disease; Gelatinase A; Vascular disease; Vascular remodeling; Peptidases; Collagen; Hydrolases; Skin; Vein; Fibroblast; Interstitial collagenase; Varix
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.0000022846.22923.46

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.