Legumain and cathepsin-L expression in human unstable carotid plaque
Legumain and cathepsin-L expression in human unstable carotid plaque
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DOI：
10.1016/j.atherosclerosis.2009.07.022
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发表时间：
2010-01-01
期刊：
影响因子：
5.3
通讯作者：
Smith, A.
中科院分区：
文献类型：
--
作者：
Mattock, K. L.;Gough, P. J.;Smith, A.
目的：半胱氨酸蛋白酶，豆科蛋白，被认为在蛋白酶如组织蛋白酶- l的加工和激活中起作用，这与斑块破裂有关。本研究旨在确定：在斑块不稳定区域，豆类活性是否上调；豆类蛋白过表达对组织蛋白酶- l活性的影响以及豆类蛋白RGD序列突变对其细胞定位的影响。方法和结果：使用一种新的ELISA和改进的活性测定法测定人颈动脉斑块提取物（n = 17）中的豆类蛋白。与相同斑块的稳定区域相比，斑块不稳定区域的豆类蛋白含量（P < 0.001）和活性（P < 0.03）是稳定区域的两倍多。使用腺病毒结构在THP-1巨噬细胞中过表达豆科蛋白导致组织蛋白酶- l从30 kDa的形式加工到25 kDa的形式。结论：斑块不稳定区域含有活性豆科蛋白水平升高。巨噬细胞中豆科蛋白的过度表达改变了组织蛋白酶- l的细胞内加工到成熟的25 kDa形式。这可能是豆类导致斑块不稳定的一种途径。2009爱思唯尔爱尔兰有限公司版权所有。
Objective: The cysteine protease, legumain, is thought to have a role in the processing and activation of proteases such as cathepsin-L, which have been implicated in plaque rupture. This study aimed to determine: if legumain activity is up-regulated in unstable areas of plaque; the effect of legumain overexpression on the activity of cathepsin-L and the effect of mutation of the legumain RGD sequence on its cellular location.Methods and results: Legumain was measured in human carotid plaque extracts (n = 17) using a novel ELISA and modified activity assay. Unstable regions of plaque contained more than twice the amount of legumain protein (P < 0.001) and activity (P < 0.03) compared with stable regions of the same plaque. Overexpression of legumain in THP-1 macrophages using an adenoviral construct resulted in the processing of cathepsin-L from its 30 kDa to its 25 kDa form compared with controls.Conclusion: Unstable regions of plaque contain increased levels of active legumain. Over-expression of legumain in macrophages alters intracellular processing of cathepsin-L to its mature 25 kDa form. This may be a means by which legumain could contribute to plaque instability. (C) 2009 Elsevier Ireland Ltd. All rights reserved.