Smooth muscle cell modulation and cytokine overproduction in varicose veins.: An in situ study

The exact aetiology and physiopathology of varicose disorders remain unclear. The aim of the present work was to study, in situ, the morphology and composition of cellular and matrix components in varicose veins compared with control veins and to identify factors that could contribute to varicose remodelling. A combined histological, immunohistochemical, and biochemical approach Nas used. Longitudinal sections of varicose (n=12) and control veins (n=9) were studied to assess the organization, structure, and phenotype of smooth muscle cells; the localization of microvascular endothelial cells; the distribution of connective tissue proteins; and the localization of cytokines. These cytokines were further quantified by ELISA. Considerable heterogeneity of the varicose vein wall was observed, with a succession of hypertrophic and atrophic segments, presenting severe disorganization of the medial layer and numerous areas of intimal thickening. In hypertrophic portions, medial smooth muscle cells showed marl;ed alterations suggesting modulation from a contractile to a proliferative and synthetic phenotype; furthermore, the number of vasa vasorum was increased, In contrast, in atrophic portions, both cellular and matrix components were decreased. TGF beta1 (p less than or equal to0.005) and bFGF (p less than or equal to 0.001) were increased and VEGF was not significantly modified in varicose veins when the results were expressed per mg of DNA. These results show that phenotypic modulation of smooth muscle cells, altered extracellular matrix metabolism, and angiogenesis are the main mechanisms contributing to the morphological and functional modifications of varicose remodelling. The increased expression of bFGF and TGF beta1 by varicose vein cells may play a pivotal role in the hypertrophy elf the venous wall, but the exact mechanism leading to aneurysmal dilatations remains to be elucidated Copyright (C) 2001 John Wiley & Sons, Ltd.