title: Notch4 is activated in endothelial and smooth muscle cells in human brain arteriovenous malformations.
abstract: 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.
authors.affiliation: 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.
authors.forename: Qichuan
authors.initials: Q
authors.lastname: ZhuGe
authors.forename: Zhebao
authors.initials: Z
authors.lastname: Wu
authors.forename: Lijie
authors.initials: L
authors.lastname: Huang
authors.forename: Bei
authors.initials: B
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.forename: WeiMing
authors.initials: W
authors.lastname: Zheng
authors.forename: Chen
authors.initials: C
authors.lastname: GouRong
authors.forename: XiaoOu
authors.initials: X
authors.lastname: Mao
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
mesh_terms: D000328:Adult; D000368:Aged; D002536:Cerebral Arteries / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D002550:Cerebral Veins / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D002648:Child; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch
keywords: AVM; Notch4; brain; human; signalling