Badier-Commander C, Couvelard A, Henin D, Verbeuren T, Michel J B, Jacob M P
INSERM U460, UFR X. Bichat, 16 Rue H. Huchard, 75870 Paris Cedex 18, France.
J Pathol. 2001 Mar;193(3):398-407. doi: 10.1002/path.819.
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.
静脉曲张性疾病的确切病因和病理生理学仍不清楚。本研究的目的是在原位研究静脉曲张与对照静脉中细胞和基质成分的形态和组成，并确定可能导致静脉曲张重塑的因素。采用了组织学、免疫组织化学和生物化学相结合的方法。研究了静脉曲张（n = 12）和对照静脉（n = 9）的纵切片，以评估平滑肌细胞的组织、结构和表型；微血管内皮细胞的定位；结缔组织蛋白的分布；以及细胞因子的定位。通过酶联免疫吸附测定法对这些细胞因子进行了进一步定量。观察到静脉曲张壁存在相当大的异质性，有一系列肥厚和萎缩段，中层严重紊乱，内膜增厚区域众多。在肥厚部分，中层平滑肌细胞显示出明显改变，提示从收缩型向增殖型和合成型表型的转变；此外，营养血管数量增加。相反，在萎缩部分，细胞和基质成分均减少。当结果以每毫克DNA表示时，静脉曲张中转化生长因子β1（p≤0.005）和碱性成纤维细胞生长因子（p≤0.001）增加，而血管内皮生长因子无明显改变。这些结果表明，平滑肌细胞的表型调节、细胞外基质代谢改变和血管生成是导致静脉曲张重塑的形态和功能改变的主要机制。静脉曲张细胞中碱性成纤维细胞生长因子和转化生长因子β1表达的增加可能在静脉壁肥厚中起关键作用，但导致动脉瘤样扩张的确切机制仍有待阐明。
