Upregulation of fibronectin and the α5β1 and αvβ3 integrins on blood vessels within the cerebral ischemic penumbra.
Upregulation of fibronectin and the α5β1 and αvβ3 integrins on blood vessels within the cerebral ischemic penumbra.
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DOI：
10.1016/j.expneurol.2011.10.017
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发表时间：
2012-01
影响因子：
5.3
通讯作者：
Milner, Richard
中科院分区：
文献类型：
--
作者：
Li, Longxuan;Liu, Fudong;Welser-Alves, Jennifer V.;McCullough, Louise D.;Milner, Richard
局灶性脑缺血后，缺血边缘或半暗带处的血管启动血管新生反应。鉴于纤维连接蛋白在血管生成中的关键作用，以及观察到在缺氧的中枢神经系统血管新生血管上纤维连接蛋白及其整合素受体的强烈上调，本研究的目的是确定在缺血的中枢神经系统中血管新生血管是否也表现出这种反应。用大脑中动脉闭塞(MCA：O)的方法建立C57/BL6小鼠的局灶性脑缺血模型，并在再灌流后7天对脑组织进行分析。在缺血核心内，免疫荧光(IF)研究显示血管表达MECA-32，泄漏脑血管的标志，以及血管破裂，定义为内皮标志CD31，以及血管黏附分子，层粘连蛋白，营养不良聚糖和α6整合素的染色缺失。在缺血半暗带内，CD31和Ki67的双重IF显示存在增殖的内皮细胞，表明正在进行的血管生成。值得注意的是，缺血半暗带血管中纤维连接蛋白及其受体α-5-β-1和α-v-β-3整合素的表达明显上调。结合我们最近发现的α-5-β-1整合素在缺氧反应中促进脑血管生成的重要作用，这些结果提示，刺激纤维连接蛋白-α-5-β-1整合素信号通路可能为放大脑缺血的内在血管生成反应提供了一种新的途径。
Following focal cerebral ischemia, blood vessels in the ischemic border, or penumbra, launch an angiogenic response. In light of the critical role for fibronectin in angiogenesis, and the observation that fibronectin and its integrin receptors are strongly upregulated on angiogenic vessels in the hypoxic CNS, the aim of this study was to establish whether angiogenic vessels in the ischemic CNS also show this response. Focal cerebral ischemia was established in C57/Bl6 mice by middle cerebral artery occlusion (MCA:O), and brain tissue analyzed seven days following re-perfusion, a time at which angiogenesis is ongoing. Within the ischemic core, immunofluorescent (IF) studies demonstrated vascular expression of MECA-32, a marker of leaky cerebral vessels, and vascular breakdown, defined by loss of staining for the endothelial marker, CD31, and the vascular adhesion molecules, laminin, dystroglycan and α6 integrin. Within the ischemic penumbra, dual-IF with CD31 and Ki67 revealed the presence of proliferating endothelial cells, indicating ongoing angiogenesis. Significantly, vessels in the ischemic penumbra showed strong upregulation of fibronectin and the fibronectin receptors, α5β1 and αvβ3 integrins. Taken together with our recent finding that the α5β1 integrin plays an important role in promoting cerebral angiogenesis in response to hypoxia, these results suggest that stimulation of the fibronectin-α5β1 integrin signalling pathway may provide a novel approach to amplifying the intrinsic angiogenic response to cerebral ischemia.
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影响因子：
3.3
作者：
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