Synthesis of collagen is dysregulated in cultured fibroblasts derived from skin of subjects with varicose veins as it is in venous smooth muscle cells.
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.


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.
Division of Angiology, Servier Research Institute, Suresnes, France.
Patricia
P
Sansilvestri-Morel
Alain
A
Rupin
Stéphane
S
Jaisson
Jean-Noël
JN
Fabiani
Tony J
TJ
Verbeuren
Paul M
PM
Vanhoutte
D000368:Aged; D002455:Cell Division; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D003470:Culture Media / Q000032:analysis; D005260:Female; D024022:Fibrillar Collagens / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis; D014648:Varicose Veins / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014680:Veins / Q000166:cytology / Q000378:metabolism
D024042:Collagen Type I; D024061:Collagen Type III; D003470:Culture Media; D024022:Fibrillar Collagens; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases