Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; Institute of Clinical & Translational Science, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
J Cell Mol Med. 2013 Nov;17(11):1458-64. doi: 10.1111/jcmm.12115. Epub 2013 Nov 5.
Up-regulation of Notch4 was observed in the endothelial cells in the arteriovenous malformations (AVMs) in mice. However, whether Notch4 is also involved in brain AVMs in humans remains unclear. Here, we performed immunohistochemistry on normal brain vascular tissue and surgically resected brain AVMs and found that Notch4 was up-regulated in the subset of abnormal vessels of the brain AVM nidus, compared with control brain vascular tissue. Two-photon confocal images show that Notch4 was expressed not only in the endothelial but also in the smooth muscle cells of the vascular wall in brain AVMs. Western blotting shows that Notch4 was activated in brain AVMs, but not in middle cerebral artery of normal human brain, which was confirmed by immunostaining. Our findings suggest a possible contribution of Notch4 signalling to the development of brain AVMs in human.
在小鼠动静脉畸形（AVM）的血管内皮细胞中观察到 Notch4 的上调。然而，Notch4 是否也参与人脑 AVM 尚不清楚。在此，我们对正常脑血管组织和手术切除的脑 AVM 进行了免疫组化染色，发现 Notch4 在脑 AVM 病灶的异常血管亚群中上调，与正常脑血管组织相比。双光子共聚焦图像显示，Notch4 不仅在脑 AVM 的血管内皮细胞中表达，也在血管壁的平滑肌细胞中表达。Western blot 显示 Notch4 在脑 AVM 中被激活，而在正常人脑的大脑中动脉中未被激活，这通过免疫染色得到了证实。我们的研究结果表明，Notch4 信号通路可能参与了人脑 AVM 的发生发展。
