Jian Liu, PhD, School of Biotechnology and Food Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui 230009, P. R. Republic of China, Tel.: +86 551 62901349, Fax:+86 551 62901331, E-mail:
Thromb Haemost. 2014 Feb;111(2):333-44. doi: 10.1160/TH13-04-0309. Epub 2013 Oct 24.
Varicose veins are a major chronic venous disease characterised by extensive remodelling of the extracellular matrix architecture in the vascular wall. Although matrix metalloproteinases have been implicated in these pathologic events, little is known about the functional relevance of other protease family members. Here, we studied the distribution of lysosomal cysteine proteases, cathepsins B, L, K, and S, and their endogenous inhibitor, cystatin C, in long saphenous vein specimens from nine normal donors and 18 patients with varicose veins (VVs). Immunohistochemical analysis demonstrated increased levels of cathepsins L, K, B, and S and reduced levels of cystatin C in VVs. This imbalance between cysteinyl cathepsins and cystatin C may favour VV remodelling. To investigate the inflammatory mechanism of their expression, we examined a detailed inflammatory cell profile in VVs, including macrophages, T lymphocytes, and mast cells. Increased numbers of CD3-positive T cells and tryptase-positive mast cells were found in VVs, and enhanced levels of cysteinyl cathepsins were detected from lesion CD3-positive T cells, chymase-positive mast cells, endothelial cells, and smooth-muscle cells. Elevated cathepsins, and their co-localisation to infiltrated inflammatory cells and to vascular cells, suggest that these proteases participate in extracellular matrix degradation in response to inflammation during VV pathogenesis.
静脉曲张是一种主要的慢性静脉疾病，其特征是血管壁细胞外基质结构的广泛重塑。虽然基质金属蛋白酶（matrix metalloproteinases）被认为与这些病理事件有关，但对于其他蛋白酶家族成员的功能相关性知之甚少。在这里，我们研究了溶酶体半胱氨酸蛋白酶（cathepsins B、L、K 和 S）及其内源性抑制剂胱抑素 C 在 9 名正常供体和 18 名静脉曲张患者的大隐静脉标本中的分布。免疫组织化学分析表明，静脉曲张组织中 cathepsins L、K、B 和 S 的水平升高，而胱抑素 C 的水平降低。这种半胱氨酸蛋白酶和胱抑素 C 之间的不平衡可能有利于静脉曲张的重塑。为了研究其表达的炎症机制，我们检查了静脉曲张中的详细炎症细胞谱，包括巨噬细胞、T 淋巴细胞和肥大细胞。在静脉曲张中发现 CD3 阳性 T 细胞和类胰蛋白酶阳性肥大细胞数量增加，并且从病变 CD3 阳性 T 细胞、糜蛋白酶阳性肥大细胞、内皮细胞和平滑肌细胞中检测到半胱氨酸蛋白酶的水平升高。升高的半胱氨酸蛋白酶及其与浸润性炎症细胞和血管细胞的共定位表明，这些蛋白酶参与了细胞外基质的降解，以响应静脉曲张发病过程中的炎症。
