Institute of Neurology (Edinger-Institute), Johann Wolfgang Goethe-University Frankfurt Medical School, Heinrich-Hoffmann-Straße 7, 60528 Frankfurt, Germany.
Exp Cell Res. 2013 May 15;319(9):1317-23. doi: 10.1016/j.yexcr.2012.12.023. Epub 2013 Jan 3.
The development of the vascular system requires orchestrated activities of various molecular pathways to assure the formation of a hierarchically branched tubular network. Furthermore, endothelial cell (EC) populations are heterogeneous to meet organ-specific requirements in the mature vasculature. This developmental scheme is probably best represented by the acquisition and maintenance of unique barrier properties known as the blood-brain barrier (BBB) in microvessels of the central nervous system (CNS). Only recently, the canonical Wnt/β-catenin pathway was implicated in many aspects of angiogenesis, vascular remodeling and differentiation in various species and organ systems. Beside its major contribution to brain angiogenesis and barrier formation, the Wnt/β-catenin pathway influences vascular sprouting, remodeling and arterio-venous specification by modulating the Notch pathway. Furthermore, canonical Wnt signaling has been implicated in heart valve formation by initiating endothelial-mesenchymal transition. Growing evidence also points to a role of the non-canonical Wnt pathway in vascular development by regulating VEGF availability. Several novel findings regarding the role of the Wnt pathway in developmental as well as in pathological angiogenesis prompted us to review its emerging function in the vasculature.
血管系统的发育需要各种分子途径的协调活动，以确保形成层次分支的管状网络。此外，内皮细胞（EC）群体是异质的，以满足成熟血管系统中特定器官的要求。这种发育方案可能最好地体现在中枢神经系统（CNS）微血管中获得和维持称为血脑屏障（BBB）的独特屏障特性上。直到最近，经典的 Wnt/β-连环蛋白途径才被认为在各种物种和器官系统的血管生成、血管重塑和分化的许多方面发挥作用。除了对脑血管生成和屏障形成的主要贡献外，Wnt/β-连环蛋白途径还通过调节 Notch 途径影响血管发芽、重塑和动静脉特化。此外，经典的 Wnt 信号通过启动内皮-间充质转化，参与心脏瓣膜形成。越来越多的证据也表明非经典 Wnt 途径在血管发育中的作用是通过调节 VEGF 的可用性来实现的。关于 Wnt 途径在发育和病理性血管生成中的作用的一些新发现促使我们回顾其在脉管系统中的新兴功能。
