Matrix metalloproteinases 2 and 9 in human atherosclerotic and non-atherosclerotic cerebral aneurysms
Matrix metalloproteinases 2 and 9 in human atherosclerotic and non-atherosclerotic cerebral aneurysms
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DOI：
10.1111/j.1468-1331.2006.01469.x
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发表时间：
2006-10-01
影响因子：
5.1
通讯作者：
Bouchier-Hayes, D.
中科院分区：
文献类型：
--
作者：
Caird, J.;Napoli, C.;Bouchier-Hayes, D.
基质金属蛋白酶2和9（MMP 2和-9）与动脉粥样硬化和动脉瘤形成的发病机制有关。本研究的目的是确定这些金属蛋白酶在人类动脉粥样硬化和非动脉粥样硬化脑动脉瘤中的作用。对11例脑动脉瘤（4例动脉粥样硬化，7例非动脉粥样硬化）进行MMP 2和MMP-9的化学染色。作为对照，动脉粥样硬化和正常的Willis动脉环进行了类似的免疫染色。所有标本均在尸检时取出并进行石蜡包埋。为了评价真实的MMP 2和-9活性，还在仅两个可用的非动脉粥样硬化性颅内动脉瘤标本中进行明胶酶谱分析，因为新鲜颅内动脉瘤组织相对不可用（即不愿在手术中切除动脉瘤基底）。我们的数据表明，MMP 2和-9在正常Willis动脉环中表达最低或根本不表达，但在动脉粥样硬化的Willis动脉环中膜平滑肌细胞中强烈表达。在动脉瘤组中，MMP 2和MMP-9在动脉粥样硬化性动脉瘤中均呈强表达，而在非动脉粥样硬化性动脉瘤中仅检测到MMP 2。酶谱显示与MMP 9标准重组蛋白相关的弱酶活性。MMP 2活性在两个标本中均未显示。这项研究表明，MMP 2和-9的表达与动脉粥样硬化有关，无论是在动脉瘤性还是非动脉瘤性脑血管中，但MMP 2似乎在没有动脉粥样硬化的动脉瘤中特异性表达，这可能表明MMP 2在动脉瘤形成期间细胞外基质的改变中发挥致病作用。
Matrix metalloproteinases 2 and 9 (MMP 2 and -9) have been implicated in the pathogenesis of atherosclerosis and aneurysm formation. The goal of the study was to establish the role of these metalloproteinases in both human atherosclerotic and non-atherosclerotic cerebral aneurysms. Eleven cerebral aneurysms (four atherosclerotic, seven non-atherosclerotic) were immunohistochemically stained for MMP 2 and -9. As controls, atherosclerotic and normal Circle of Willis arteries were similarly immunostained. All specimens were retrieved at autopsy and were paraffin-embedded. In order to evaluate the real MMP 2 and -9 activities, gelatin zymography was also performed in only two available specimens of non-atherosclerotic intracranial aneurysms, because of the relative unavailability of fresh intracranial aneurysm tissue (i.e. reluctance to excise the aneurysm fundus at surgery). Our data establish that MMP 2 and -9 were expressed minimally or not at all in normal Circle of Willis arteries but were strongly expressed in medial smooth muscle cells of atherosclerotic Circle of Willis arteries. In the aneurysm group, both MMP 2 and -9 were strongly expressed in the atherosclerotic aneurysms, but MMP 2 alone was detected in the non-atherosclerotic aneurysms. Zymography revealed a weak enzyme activity correlating to MMP 9 standard recombinant protein. MMP 2 activity was not demonstrated in either specimen. This study shows that the expression of MMP 2 and -9 is associated with atherosclerosis, be it in aneurysmal or non-aneurysmal cerebral vessels but MMP 2 appears to be specifically expressed in aneurysms devoid of atherosclerosis perhaps suggesting a pathogenic role for MMP 2 in the alteration of the extracellular matrix of cerebral arteries during aneurysm formation.