O'Hare Michael, Arboleda-Velasquez Joseph F
Department of Ophthalmology at Harvard Medical School, Schepens Eye Research Institute of Mass Eye and Ear, Boston, Massachusetts 02114, USA.
Cold Spring Harb Perspect Med. 2022 May 9;12(9). doi: 10.1101/cshperspect.a041159.
The Notch signaling pathway is a highly versatile and evolutionarily conserved mechanism with an important role in cell fate determination. Notch signaling plays a vital role in vascular development, regulating several fundamental processes such as angiogenesis, arterial/venous differentiation, and mural cell investment. Aberrant Notch signaling can result in severe vascular phenotypes as observed in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Alagille syndrome. It is known that vascular endothelial cells and mural cells interact to regulate vessel formation, cell maturation, and stability of the vascular network. Defective endothelial-mural cell interactions are a common phenotype in diseases characterized by impaired vascular integrity. Further refinement of the role of Notch signaling in the vascular junctions will be critical to attempts to modulate Notch in the context of human vascular disease. In this review, we aim to consolidate and summarize our current understanding of Notch signaling in the vascular endothelial and mural cells during development and in the adult vasculature.
Notch信号通路是一种高度通用且在进化上保守的机制，在细胞命运决定中起重要作用。Notch信号在血管发育中起着至关重要的作用，调节着诸如血管生成、动脉/静脉分化和壁细胞募集等几个基本过程。异常的Notch信号可导致严重的血管表型，如在伴有皮质下梗死和白质脑病的大脑常染色体显性动脉病（CADASIL）和阿拉吉尔综合征中所观察到的。已知血管内皮细胞和壁细胞相互作用以调节血管形成、细胞成熟和血管网络的稳定性。内皮-壁细胞相互作用缺陷是血管完整性受损疾病的常见表型。进一步明确Notch信号在血管连接处的作用对于在人类血管疾病背景下调节Notch的尝试至关重要。在本综述中，我们旨在巩固和总结我们目前对发育过程中以及成人脉管系统中血管内皮细胞和壁细胞中Notch信号的理解。
