Linking Notch signaling to ischemic stroke
Linking Notch signaling to ischemic stroke
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DOI：
10.1073/pnas.0709867105
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发表时间：
2008-03-25
影响因子：
11.1
通讯作者：
Artavanis-Tsakonas, Spyros
中科院分区：
文献类型：
--
作者：
Arboleda-Velasquez, Joseph F.;Zhou, Zhipeng;Artavanis-Tsakonas, Spyros
血管平滑肌细胞（SMCs）与中风的病理生理有关，中风是世界上第三大常见死亡原因和长期神经功能障碍的主要原因。然而，对SMC功能与脑缺血易感性之间的潜在细胞通路知之甚少。利用迄今为止尚未表征的Notch 3敲除小鼠模型，我们发现了Notch信号受体旁链在血管SMCs中高度表达时对缺血性中风的惊人易感性。来源于这些动物的血管SMCs的细胞和分子分析将Notch 3活性与特定基因靶点的表达联系起来，而遗传拯救实验则明确地将血管中的Notch 3功能与缺血表型联系起来。
Vascular smooth muscle cells (SMCs) have been implicated in the pathophysiology of stroke, the third most common cause of death and the leading cause of long-term neurological disability in the world. However, there is little insight into the underlying cellular pathways that link SMC function to brain ischemia susceptibility. Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype.