Notch4 is activated in endothelial and smooth muscle cells in human brain arteriovenous malformations

作者:ZhuGe Qichuan*; Wu Zhebao; Huang Lijie; Zhao Bei; Zhong Ming; Zheng WeiMing; Chen GouRong; Mao XiaoOu; Xie Lin; Wang Xiangdong; Jin Kunlin
来源:JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2013, 17(11): 1458-1464.
DOI:10.1111/jcmm.12115

摘要

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.