Varicose vein disease is a frequently occurring pathology with multifactorial causes and a genetic component. An intense remodelling of the varicose vein wall has been described and could be at the origin of its weakness and altered elasticity. We have described previously a dysregulation of collagen synthesis in cultured smooth muscle cells from saphenous veins and in dermal fibroblasts from the skin of patients with varicose veins, suggesting a systemic defect in their connective tissue. The present study describes comparative morphological and immunohistochemical data in both the skin and saphenous veins of eight control subjects (undergoing coronary bypass surgery) and eight patients with varicose veins. Histological staining of glycoproteins, the elastic fibre network and collagen bundles showed that the remodelling and fragmentation of elastic fibres observed in varicose veins were also present in the skin of the patients. When compared with control subjects, we observed in both the veins and skin of patients with varicose veins (i) an increase in the elastic network, as quantified by image analysis; (ii) an accumulation of collagen type I, fibrillin-1 and laminin; and (iii) an overproduction of MMP (matrix metalloproteinase)-1, MMP-2 and MMP-3, analysed by immunohistochemistry, but normal levels of other MMPs (MMP-7 and MMP-9) and their inhibitors (TIMP-1, TIMP-2 and TIMP-3). An imbalance of extracellular matrix production/degradation was thus observed in veins as well as in the skin of the patients with varicose veins and, taken together, these findings show that remodelling is present in different organs, confirming systemic alterations of connective tissues.

译文

静脉曲张疾病是一种常见的病理,具有多因素原因和遗传因素。已经描述了静脉曲张壁的强烈重塑,这可能是其弱点和弹性改变的根源。我们先前已经描述了来自大隐静脉的培养平滑肌细胞和来自静脉曲张患者皮肤的真皮成纤维细胞中胶原蛋白合成的失调,表明其结缔组织存在全身性缺陷。本研究描述了八名对照受试者 (接受冠状动脉搭桥手术) 和八名静脉曲张患者的皮肤和隐静脉的比较形态学和免疫组织化学数据。糖蛋白,弹性纤维网络和胶原束的组织学染色表明,在静脉曲张中观察到的弹性纤维的重塑和断裂也存在于患者的皮肤中。与对照组相比,我们在静脉曲张患者的静脉和皮肤中观察到 (i) 通过图像分析量化的弹性网络的增加; (ii) I型胶原,fibrillin-1和层粘连蛋白的积累; (iii) 通过免疫组织化学分析MMP-2和MMP-3的MMP (基质金属蛋白酶)-1的过量生产,但其他MMP (MMP-7和MMP-9) 及其抑制剂 (TIMP-1,TIMP-2和TIMP-3) 的正常水平。因此,在静脉曲张患者的静脉以及皮肤中观察到细胞外基质产生/降解的不平衡,这些发现共同表明,重塑存在于不同器官中,从而证实了结缔组织的全身性改变。

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