Kofler Natalie M, Simons Michael
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine 300 George Street, New Haven, CT 06520 USA.
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine 300 George Street, New Haven, CT 06520 USA ; Department of Cell Biology, Yale University School of Medicine 300 George Street, New Haven, CT 06520 USA.
F1000Prime Rep. 2015 Mar 3;7:26. doi: 10.12703/P7-26. eCollection 2015.
In development and disease, vascular endothelial growth factor (VEGF) regulates the expansion of the vascular tree. In response to hypoxia, VEGF promotes new capillary formation through the process of angiogenesis by inducing endothelial cell sprouting, proliferation, and migration. Wound healing, tissue regeneration, and tumor growth depend on angiogenesis for adequate nutrient and oxygen delivery. Under different conditions, VEGF promotes arterial growth, modulates lumen expansion, and induces collateral vessel formation, events collectively referred to as arteriogenesis. Induction of arteriogenesis after cardiac or cerebral arterial occlusion can reduce ischemia and improve disease outcome. Endothelial VEGF receptor 2 (VEGFR2) signaling governs both processes. However, modulation of downstream VEGF signaling effectors, such as extracellular-signal-regulated kinase (ERK) activation, differs in order to achieve angiogenic versus arteriogenic outcomes. Recent reports show that neuropilin 1 (NRP1), a VEGF receptor, can instill VEGF signaling outcomes that specifically regulate either angiogenesis or arteriogenesis. Here, we discuss how NRP1 functions as a VEGFR2 co-receptor in angiogenesis and a modulator of VEGFR2 trafficking in arteriogenesis. The unique role played by neuropilin in different endothelial processes makes it an exciting therapeutic target to specifically enhance angiogenesis or arteriogenesis in disease settings.
在发育和疾病过程中，血管内皮生长因子（VEGF）调节血管树的扩张。在缺氧反应中，VEGF通过诱导内皮细胞发芽、增殖和迁移，促进血管生成过程中形成新的毛细血管。伤口愈合、组织再生和肿瘤生长都依赖血管生成来提供充足的营养和氧气。在不同条件下，VEGF促进动脉生长、调节管腔扩张并诱导侧支血管形成，这些事件统称为动脉生成。心脏或脑动脉闭塞后诱导动脉生成可减轻缺血并改善疾病预后。内皮VEGF受体2（VEGFR2）信号传导控制这两个过程。然而，为了实现血管生成与动脉生成的结果，下游VEGF信号效应器的调节（如细胞外信号调节激酶（ERK）激活）有所不同。最近的报告表明，VEGF受体神经纤毛蛋白1（NRP1）可以赋予VEGF信号传导结果，特异性调节血管生成或动脉生成。在这里，我们讨论NRP1如何在血管生成中作为VEGFR2共受体发挥作用，以及在动脉生成中作为VEGFR2转运的调节剂。神经纤毛蛋白在不同内皮过程中所起的独特作用使其成为在疾病环境中特异性增强血管生成或动脉生成的一个令人兴奋的治疗靶点。
