Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) in cerebral cavernous malformations: immunohistochemical analysis of MMP-2,-9 and TIMP-2
Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) in cerebral cavernous malformations: immunohistochemical analysis of MMP-2,-9 and TIMP-2
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DOI：
10.1007/s00701-006-0929-8
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发表时间：
2007-02-01
影响因子：
2.4
通讯作者：
Tominaga, T.
中科院分区：
文献类型：
--
作者：
Fujimura, M.;Watanabe, M.;Tominaga, T.
Object.脑血管畸形（如脑海绵状血管畸形（CCM））出血可导致显著的死亡率和发病率，但其潜在机制尚未确定。基质金属蛋白酶（MMP）（降解细胞外基质的所有组分的蛋白水解酶）对血管基质的过度降解可导致血管结构的不稳定性，从而可引起出血。因此，我们检测了基质金属蛋白酶和金属蛋白酶组织抑制剂（TIMP）在CCM中的表达。我们对7例CCM患者手术标本的石蜡包埋切片进行MMP-2、MMP-9和TIMP-2的免疫组化。所有患者均有CCM出血史。MMP-2和MMP-9在所有患者（7/7，100%）的CCM内皮细胞中呈强表达。在所有7名患者中，TIMP-2的内皮表达也很明显。MMP-2、MMP-9和TIMP-2在正常脑组织中均未表达。我们发现CCM显示MMP-2、-9和TIMP-2的内皮表达增加。MMP和/或TIMP的内皮表达可能影响血管基质的稳定性，从而可能导致CCM出血。
Object. Hemorrhage from cerebral vascular malformations such as cerebral cavernous malformation (CCM) can result in significant mortality and morbidity, but its underlying mechanism is undetermined. Excessive degradation of the vascular matrix by matrix metalloproteinases (MMPs), proteolytic enzymes that degrade all the components of extracellular matrix, can lead to instability of the vascular structure and can thereby cause bleeding. Thus we examined the expression of MMPs and tissue inhibitors of metalloproteinase (TIMP) in CCM.Patients and methods. We performed immunohistochemistry for MMP-2, -9, and TIMP-2 using Paraffin-embedded sections of the surgical specimens obtained from seven patients with CCM. All patients had a history of hemorrhage from CCM.Findings. In all patients (7/7, 100%), MMP-2 and -9 were strongly expressed in endothelial cells of CCMs. Endothelial expression of TIMP-2 was also evident in all seven patients. In contrast, MMP-2, -9 and TIMP-2 were not identified in adjacent normal brain tissue.Conclusion. We found that CCM showed the increased endothelial expression of MMP-2, -9, and TIMP-2. Endothelial expression of MMPs and/or TIMP may affect the vascular matrix stability, and thus can contribute to hemorrhage from CCM.