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 was 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 marked 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. TGFbeta1 (p< or =0.005) and bFGF (p< or =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 TGFbeta1 by varicose vein cells may play a pivotal role in the hypertrophy of the venous wall, but the exact mechanism leading to aneurysmal dilatations remains to be elucidated.

Varicose veins have a thickening wall. Their smooth muscle cells are disorganized as regards proliferation and production of extracellular matrix protein. An imbalance between the synthesis of collagen type I protein (collagen I) and collagen type III protein (collagen III) could explain the lack of elasticity of varicose veins. Therefore, collagen synthesis was compared in the media and in cultured smooth muscle cells derived from human control and varicose saphenous veins. An increase in total collagen synthesis was observed in the media and in smooth muscle cells derived from varicose veins. This augmentation was due to an overproduction of collagen I in cultured cells from varicose veins consistent with an increase in the release of collagen I metabolites in the media. A concomitant decrease in collagen III was observed in cultures of smooth muscle cells from varicose veins. The increase in the synthesis of collagen I in cells from varicose veins was correlated with an overexpression of the gene since mRNAs for collagen I were augmented without change in mRNA-half-life. This augmentation in the synthesis of collagen I was reduced by the addition of exogenous collagen III in cultures from varicose veins. These findings suggest a dysregulation of the synthesis of collagen I and III in smooth muscle cells derived from varicose veins.

In mature spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), acetylcholine and the calcium ionophore A-23187 release endothelium-derived contracting factors (EDCFs), cyclooxygenase derivatives that activate thromboxane-endoperoxide (TP) receptors on vascular smooth muscle. The EDCFs released by acetylcholine are most likely prostacyclin and prostaglandin (PG)H(2), whereas those released by A-23187 remain to be identified. Isometric tension and the release of PGs were measured in rings of isolated aortas of WKY and SHR. A-23187 evoked the endothelium-dependent release of prostacyclin, thromboxane A(2), PGF(2alpha), PGE(2), and possibly PGH(2) (PGI(2) >> thromboxane A(2) = PGF(2alpha) = PGE(2)). In SHR aortas, the release of prostacyclin and thromboxane A(2) was significantly larger in response to A-23187 than to acetylcholine. In response to the calcium ionophore, the release of thromboxane A(2) was significantly larger in aortas of SHR than in those of WKY. In both strains of rat, the inhibition of cyclooxygenase-1 prevented the release of PGs and the occurrence of endothelium-dependent contractions. Dazoxiben, the thromboxane synthase inhibitor, abolished the A-23187-dependent production of thromboxane A(2) and inhibited by approximately one-half the endothelium-dependent contractions. U-51605, an inhibitor of PGI synthase, reduced the release of prostacyclin elicited by A-23187 but induced a parallel increase in the production of PGE(2) and PGF(2alpha), suggestive of a PGH(2) spillover, which was associated with the enhancement of the endothelium-dependent contractions. These results indicate that in the aorta of SHR and WKY, the endothelium-dependent contractions elicited by A-23187 involve the release of thromboxane A(2) and prostacyclin with a most likely concomitant contribution of PGH(2).

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Stent implantation results in more intense and sustained expression of MMP9 and activation of MMP2 than balloon angioplasty.