Plein Alice, Fantin Alessandro, Ruhrberg Christiana
UCL Institute of Ophthalmology, University College London, London, UK.
Microcirculation. 2014 May;21(4):315-23. doi: 10.1111/micc.12124.
The formation of the cardiovasculature, consisting of both the heart and blood vessels, is a critical step in embryonic development and relies on three processes termed vasculogenesis, angiogenesis, and vascular remodeling. The transmembrane protein NRP1 is an essential modulator of embryonic angiogenesis with additional roles in vessel remodeling and arteriogenesis. NRP1 also enhances arteriogenesis in adults to alleviate pathological tissue ischemia. However, in certain circumstances, vascular NRP1 signaling can be detrimental, as it may promote cancer by enhancing tumor angiogenesis or contribute to tissue edema by increasing vascular permeability. Understanding the mechanisms of NRP1 signaling is, therefore, of profound importance for the design of therapies aiming to control vascular functions. Previous work has shown that vascular NRP1 can variably serve as a receptor for two secreted glycoproteins, the VEGF-A and SEMA3A, but it also has a poorly understood role as an adhesion receptor. Here, we review current knowledge of NRP1 function during blood vessel growth and homeostasis, with special emphasis on the vascular roles of its multiple ligands and signaling partners.
由心脏和血管组成的心血管系统的形成是胚胎发育中的关键步骤，它依赖于血管生成、血管新生和血管重塑这三个过程。跨膜蛋白神经纤毛蛋白1（NRP1）是胚胎血管新生的重要调节因子，在血管重塑和动脉生成中也发挥着额外作用。NRP1还可增强成体中的动脉生成，以缓解病理性组织缺血。然而，在某些情况下，血管NRP1信号可能是有害的，因为它可能通过增强肿瘤血管新生促进癌症，或者通过增加血管通透性导致组织水肿。因此，了解NRP1信号传导机制对于设计旨在控制血管功能的疗法至关重要。先前的研究表明，血管NRP1可以作为两种分泌糖蛋白——血管内皮生长因子A（VEGF-A）和3A类信号素（SEMA3A）的受体，但它作为黏附受体的作用却鲜为人知。在此，我们综述了目前关于NRP1在血管生长和稳态过程中功能的认识，特别强调了其多种配体和信号伴侣的血管作用。
