Increased levels of lysosomal cysteinyl cathepsins in human varicose veins: A histology study
Increased levels of lysosomal cysteinyl cathepsins in human varicose veins: A histology study
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人静脉曲张中溶酶体半胱氨酰组织蛋白酶水平升高：组织学研究
DOI：
10.1160/th13-04-0309
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发表时间：
2013-10
影响因子：
6.7
通讯作者：
Jian Liu
中科院分区：
文献类型：
--
作者：
Bin Bao;Lei Zheng;Guo-Ping Shi;Jian Liu
摘要静脉曲张是一种主要的慢性静脉疾病，其特征是血管壁上广泛的细胞外基质结构重构。尽管基质金属蛋白酶参与了这些病理事件，但对其他蛋白水解酶家族成员的功能相关性知之甚少。本文对9例正常人和18例静脉曲张患者的大隐长静脉标本中溶酶体半胱氨酸蛋白酶、组织蛋白B、L、K和S及其内源性抑制物半胱氨酸蛋白酶C的分布进行了研究。免疫组织化学分析显示，VVS组织中组织蛋白L、K、B和S的水平升高，而胱抑素C的水平降低。这种半胱氨酸基组织蛋白和半胱氨酸蛋白酶C之间的失衡可能有利于VV重塑。为了研究它们表达的炎症机制，我们检查了VVS中详细的炎症细胞图谱，包括巨噬细胞、T淋巴细胞和肥大细胞。VVS中CD3阳性T细胞和类胰蛋白酶阳性肥大细胞数量增加，病变中CD3阳性T细胞、糜酶阳性肥大细胞、内皮细胞和平滑肌细胞半胱氨酸组织蛋白水平升高。组织蛋白的升高，以及它们与浸润性炎症细胞和血管细胞的共定位，表明这些蛋白参与了VV发病过程中炎症反应的细胞外基质降解。
Summary 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.
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DOI：
10.1161/01.atv.18.11.1707
发表时间：
1998-11-01
影响因子：
8.7
作者：
Johnson, JL;Jackson, CL;George, SJ
通讯作者：
George, SJ
影响因子：
15.9
作者：
Sukhova, GK;Zhang, Y;Shi, GP
通讯作者：
Shi, GP
DOI：
10.1016/s0021-9258(17)32427-4
发表时间：
1994-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Saarinen;N. Kalkkinen;H. Welgus;P. Kovanen
通讯作者：
J. Saarinen;N. Kalkkinen;H. Welgus;P. Kovanen
影响因子：
2.5
作者：
B. Halloran;B. Baxter
通讯作者：
B. Halloran;B. Baxter
影响因子：
7.3
作者：
Badier-Commander, C;Couvelard, A;Jacob, MP
通讯作者：
Jacob, MP