Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage
Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage
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DOI：
10.1016/j.jns.2004.11.041
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发表时间：
2005-03-15
影响因子：
4.4
通讯作者：
Xu, J
中科院分区：
文献类型：
--
作者：
Lee, JM;Yin, KJ;Xu, J
自发性脑内出血（ICH）是脑淀粉样血管病（CAA）最常见的并发症之一，但对这种危及生命的并发症的分子发病机制知之甚少。在这篇综述中，我们提出了初步的证据表明，细胞外基质降解蛋白酶，基质金属蛋白酶-9（MMP-9），可能发挥作用的发展自发性脑出血导致CAA。淀粉样β肽（A β）诱导小鼠脑内皮细胞（CEC）中MMP-9的合成、细胞释放和活化，导致细胞外基质（ECM）降解增加。此外，在CAA（APPsw转基因小鼠）的小鼠模型中，MMP-9免疫反应性在老年APPsw小鼠的淀粉样蛋白负载的脑血管中观察到，但在年轻的APPsw或老年野生型小鼠。更广泛的MMP-9免疫染色存在于淀粉样蛋白负载的血管与微出血的证据。这些结果表明，血管MMP-9的表达增加，刺激A，可能在CAA患者自发性脑出血（ICH）的发病机制中发挥作用。(c)2004 Elsevier B. V.保留所有权利。
Spontaneous intracerebral hemorrhage (ICH) is one of the most recognized complications of cerebral amyloid angiopathy (CAA), but little is known about the molecular pathogenesis of this life-threatening complication. In this review, we present preliminary evidence which suggests that the extracellular-matrix-degrading protease, matrix metalloprotemase-9 (MMP-9), may play a role in the development of spontaneous ICH resulting from CAA. The amyloid-beta peptide (A beta) induced the synthesis, cellular release, and activation of MMP-9 in murine cerebral endothelial cells (CECs), resulting in increased extracellular matrix (ECM) degradation. Furthermore, in a mouse model of CAA (APPsw transgenic mice), MMP-9 immunoreactivity was observed in amyloid-laden cerebral vessels in aged APPsw mice but not in young APPsw or aged wild-type mice. More extensive MMP-9 immunostaining was present in amyloid-laden vessels with evidence of microhemorrhage. These results suggest that increased vascular MMP-9 expression, stimulated by A, may play a role in the pathogenesis of spontaneous intracerebral hemorrhage (ICH) in patients with CAA. (c) 2004 Elsevier B.V. All rights reserved.