Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells
Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells
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DOI：
10.1016/j.atherosclerosis.2005.05.012
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发表时间：
2006-02-01
期刊：
影响因子：
5.3
通讯作者：
Shi, GP
中科院分区：
文献类型：
--
作者：
Liu, J;Sukhova, GK;Shi, GP
半胱氨酸蛋白酶L是哺乳动物中最有效的弹性蛋白酶和胶原酶之一，在大多数组织和细胞类型的基础水平上广泛表达，并受促炎刺激的调节。炎症性动脉疾病、腹主动脉瘤(AAA)和动脉粥样硬化涉及广泛的血管重塑，需要弹性溶解和胶原溶解。本研究验证了组织蛋白酶L在人腹主动脉瘤和动脉粥样硬化病变中过表达的假说，并且在这些病变中发现的血管细胞类型中组织蛋白酶L的表达受促炎细胞因子的调节。免疫组织化学和组织提取免疫印迹分析显示，组织蛋白酶L在人腹主动脉瘤和动脉粥样硬化中的表达增加，并定位于病变的平滑肌细胞、内皮细胞和巨噬细胞。在原代培养的人SMC、EC和单核细胞来源的巨噬细胞中，促炎细胞因子或生长因子诱导组织蛋白酶L的表达及其对抗细胞外胶原和弹性蛋白的活性。冠状动脉狭窄组(n=65)血清组织蛋白酶L水平明显高于冠状动脉造影组(n=30)(1.47±0.33 ng/mlvs 0.60±0.06 ng/ml，p<；0.02)。冠脉狭窄患者左前降支狭窄程度与血清组织蛋白酶L水平呈显著正相关(R=0.542，p<；0.0001)，提示组织蛋白酶L参与了这些血管疾病的发生。(C)2005爱思唯尔爱尔兰有限公司。保留所有权利。
The cysteine protease cathepsin L is one of the most potent mammalian elastases and collagenases, widely expressed at basal levels in most tested tissues and cell types, and regulated by pro-inflammatory stimuli. The inflammatory arterial diseases abdominal aortic aneurysm (AAA) and atherosclerosis involve extensive vascular remodeling that requires elastolysis and collagenolysis. This study examined the hypothesis that cathepsin L is over-expressed in human AAA and atherosclerotic lesions and its expression in vascular cell types found in these lesions is regulated by pro-inflammatory cytokines. Immunohistochemical and tissue extract immunoblot analysis demonstrated increased expression of cathepsin L in human AAA and atheromata and localized its expression to lesional smooth muscle cells (SMC), endothelial cells (EC), and macrophages. In primary cultured human SMC, EC, and monocyte-derived macrophages, pro-inflammatory cytokines or growth factors induced the expression of cathepsin L and its activity against extracellular collagen and elastin. Patients with coronary artery stenosis (n = 65) had higher serum cathepsin L levels than those without lesions detectable by quantitative coronary angiography (n = 30) (1.47 +/- 0.33 ng/ml versus 0.60 +/- 0.06 ng/ml, p < 0.02). A strong correlation between the percent of stenosis of left anterior descending coronary artery and serum cathepsin L levels in patients with stenosis (R = 0.542, p < 0.0001), also suggests involvement of cathepsin L in these vascular diseases. (c) 2005 Elsevier Ireland Ltd. All rights reserved.