Upregulation of tissue inhibitor of metalloproteinase-1 contributes to restoration of the extracellular matrix in the rabbit basilar artery during cerebral vasospasm after subarachnoid hemorrhage
Upregulation of tissue inhibitor of metalloproteinase-1 contributes to restoration of the extracellular matrix in the rabbit basilar artery during cerebral vasospasm after subarachnoid hemorrhage
复制标题
DOI：
10.1016/j.brainres.2015.04.049
复制
发表时间：
2015-08-07
期刊：
影响因子：
2.9
通讯作者：
Sasaki, Tomio
中科院分区：
文献类型：
--
作者：
Kurogi, Ryota;Kikkawa, Yuichiro;Sasaki, Tomio
细胞外基质（ECM）代谢引起的血管重构参与蛛网膜下腔出血（SAH）后脑血管痉挛的发生。组织金属蛋白酶抑制剂（TIMPs）和基质金属蛋白酶（MMPs）之间的平衡在ECM重塑中起着重要作用。我们研究了兔双出血模型脑血管痉挛后血管重构的机制。兔基底动脉在初次出血后第3、5、7天切除。采用微阵列分析、实时定量PCR、免疫印迹分析和酶联免疫吸附试验（ELISA）检测TIMP-1、TIMP-2、MMP-2和MMP-9 mRNA和蛋白的表达。免疫组织化学染色检测TIMP-1、TIMP-2、MMP-2、MMP-9、弹性蛋白、纤维连接蛋白、层粘连蛋白、I、III、IV胶原的表达和定位。SAH后，TIMP-1 mRNA和蛋白的表达在第3天显著升高，在第5天和第7天降至对照水平。第7天MMP-9蛋白表达显著升高。第7天，TIMP-2、MMP-2 mRNA和蛋白表达量显著升高。弹性蛋白、纤维连接蛋白、层粘连蛋白和胶原I、III、IV蛋白的表达在第3天降低，第7天恢复到对照水平。脑血管痉挛早期TIMP-1的上调可能有助于脑血管痉挛晚期ECM的恢复，从而发挥TIMP-1对脑血管痉挛的保护作用。此外，脑血管痉挛早期ECM的减少增加了动脉顺应性，可能促进了脑动脉的血管收缩。(C) 2015 Elsevier B.V.版权所有
Vascular remodeling caused by extracellular matrix (ECM) metabolism contributes to the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). The balance between tissue inhibitor of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) plays an important role in ECM remodeling. We investigated the mechanism of vascular remodeling following cerebral vasospasm in a rabbit double hemorrhage model. Rabbit basilar arteries were harvested on days 3, 5, and 7 after initial hemorrhage. TIMP-1, TIMP-2, MMP-2, and MMP-9 mRNA and protein expression were investigated with microarray analysis, quantitative real-time PCR, immunoblot analysis, and enzyme-linked immunosorbent assay (ELISA). The expression and localization of TIMP-1, TIMP-2, MMP-2, MMP-9, elastin, fibronectin, laminin, and collagens I, III, and IV were investigated with immuohistochemical staining. After SAH, TIMP-1 mRNA and protein expression were significantly increased on day 3 and then decreased to the control level on days 5 and 7. MMP-9 protein expression was significantly increased on day 7. TIMP-2 and MMP-2 mRNA and protein expression were significantly increased on day 7. Elastin, fibronectin, laminin, and collagens I, III, and IV protein expression was decreased on day 3 and then restored to control levels on day 7. Upregulation of TIMP-1 during the early phase of cerebral vasospasm may contribute to the recovery of the ECM during the late phase of cerebral vasospasm, resulting in a protective role of TIMP-1 from cerebral vasospasm. Moreover, the increase in arterial compliance by the decrease in ECM during the early phase of cerebral vasospasm may facilitate vasoconstriction of the cerebral artery. (C) 2015 Elsevier B.V. All rights reserved.