Alterations in Smooth Muscle Cells Dermal Fibroblasts and Collagen

Several studies have investigated cultured smooth muscle cells derived from varicose veins to determine if the extracellular matrix modifications seen in varicose vein tissue are related to smooth muscle cells. Smooth muscle cells cultured from varicose veins were found to have decreased number of cells staining for collagen type III and fibronectin, although the transcriptional products of these two proteins were not dissimilar. The synthesis and deposition of collagen type III but not type I was significantly lower in varicose veins. When MMPs and TIMPs were analyzed from the supernatant of confluent cells no differences were observed. These findings suggested that the regulation was altered during posttranscriptional events for both collagen type III and fibronectin in smooth muscle cells.10 Further work in this area demonstrated that varicose greater saphenous vein has a smaller spiraled collagen distribution specifically in the intima and media.

In an interesting study, investigators evaluated cultured dermal fibroblasts collagen abnormalities, to determine if the phenotypic changes observed in venous smooth muscle cells of patients with varicose veins are also present in their dermal fibroblasts. The findings from this study demonstrated that the synthesis of collagen type I and the transcript mRNA product were increased in dermal fibroblasts, but as in smooth muscle cells, dermal fibroblasts also had decreased synthesis of collagen type III despite normal transcript. Among the various MMPs evaluated, pro-MMP-2 was increased in dermal fibroblasts cultured from patients with venous disease. The authors concluded that the synthesis of collagen type III is dysregulated in dermal fibroblasts and is comparable to the observations of smooth muscle cells derived from patients with varicose veins, suggesting a systemic alteration in tissue remodeling.11 The same investigators demonstrated that with inhibition of MMP with Marimastat, the production of collagen type III in smooth muscle cells from varicose veins was partially restored. In addition MMP-3, which degrades fibronectin, was elevated in both transcription product and protein expression. The authors concluded that the mechanism involved in collagen type III and fibronectin degradation in the smooth muscle cells cultured from varicose veins likely is linked to the expression of MMP-3.

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