TIMP-2 and PAI-1 mRNA levels are lower in aneurysmal as compared to athero-occlusive abdominal aortas
TIMP-2 and PAI-1 mRNA levels are lower in aneurysmal as compared to athero-occlusive abdominal aortas
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DOI：
10.1016/s0008-6363(03)00513-3
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发表时间：
2003-10-15
影响因子：
10.8
通讯作者：
Sakalihasan, N
中科院分区：
文献类型：
--
作者：
Defawe, OD;Colige, A;Sakalihasan, N
目的：腹主动脉瘤（AAA）和动脉粥样硬化闭塞症（AOD）的血管壁发生显著改变，最终可能导致血管破裂或阻塞。这些修改已被归因于一个或一组蛋白酶，其抑制剂或参与修复过程的基质大分子，而不考虑所观察到的变化的程度。研究方法：大范围蛋白水解酶的mRNA稳态水平（基质金属蛋白酶：MMP-1、-2、-3、-8、-9、-11、-12、-13、-14;尿激酶纤溶酶原激活物：u-PA），它们的生理抑制剂（MMP的组织抑制剂：TIMP-1、TIMP-2、TIMP-3;纤溶酶原激活物抑制剂：派-1）和结构基质蛋白（I型和III型胶原蛋白、核心蛋白聚糖、弹性蛋白、原纤维蛋白1和2）的含量通过RT-PCR测定，通过在每种反应混合物中使用合成RNA作为内标进行定量。在AAA（n=7）和AOD（n=5）中评估表达谱，并与非病变腹主动脉（CAA，n=7）和胸主动脉（CTA n=5）进行比较。结果如下：与炎性细胞相关的MMPs-8、-9、-12和-13在CAA和CTA中未检测到或几乎未检测到，而在AAA和AOD中大量表达且相似。蛋白酶抑制剂或结构蛋白的表达仅略有增加，在这两种病理条件下，与弹性蛋白，这是减少例外。AAA与AOD之间的主要差异是TIMP-2和派-1在瘤样病变中的表达较低。结论：AAA和AOD中主动脉壁的重塑涉及蛋白水解酶的大量和相似谱的基因激活，而两种生理抑制剂TIMP-2和派-1的表达在AAA中显著低于AOD。动脉瘤的修复过程与闭塞性病变相似。(C)2003年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: Significant alterations of the vascular wall occurs in abdominal aortic aneurysm (AAA) and atherosclerotic occlusive disease (AOD) that ultimately may lead to either vascular rupture or obstruction. These modifications have been ascribed to one or a group of proteases, their inhibitors or to the matrix macromolecules involved in the repair process without considering the extent of the observed variations. Methods: The mRNA steady-state level of a large spectrum of proteolytic enzymes (matrix metalloproteinases: MMP-1, -2, -3, -8, -9, -11, -12, -13, -14; urokinase plasminogen activator: u-PA), their physiological inhibitors (tissue inhibitors of MMPs: TIMP-1, -2, -3; plasminogen activator inhibitor: PAI-1) and that of structural matrix proteins (collagens type I and III, decorin, elastin, fibrillins 1 and 2) was determined by RT-PCR made quantitative by using a synthetic RNA as internal standard in each reaction mixture. The profile of expression was evaluated in AAA (n=7) and AOD (n=5) and compared to non-diseased abdominal (CAA, n=7) and thoracic aorta (CTA n=5). Results: The MMPs -8, -9, -12 and -13 mostly associated with inflammatory cells were not or barely detected in CAA and CTA while they were largely and similarly expressed in AAA and AOD. Expression of protease inhibitors or structural proteins were only slightly increased in both pathological conditions with the exception of elastin which was reduced. The main significant difference between AAA and AOD was a lower expression of TIMP-2 and PAI-1 in the aneurysmal lesions. Conclusions: The remodeling of the aortic wall in AAA and AOD involves gene activation of a large and similar spectrum of proteolytic enzymes while the expression of two physiological inhibitors, TIMP-2 and PAI-1, is significantly lower in AAA compared to AOD. The repair process in the aneurysmal disease seems similar to that of the occlusive disease. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.