Mandriota S J, Pepper M S
Centre Médical Universitaire, Département de Morphologie, Genève, Suisse.
J Soc Biol. 1999;193(2):159-63.
Vascular endothelial growth factor (VEGF)-C is a new member of the VEGF family, a group of polypeptide growth factors which play key roles in the physiology and pathology of many aspects of the cardiovascular system, including vasculogenesis, hematopoiesis, angiogenesis and vascular permeability. VEGF signalling in endothelial cells occurs through three tyrosine kinase receptors (VEGFRs), expressed by endothelial cells and hematopoietic precursors. With respect to the first VEGF described, VEGF-A, which is an endothelial cell specific mitogen and key angiogenic factor, VEGF-C seems to play a major role in the development of the lymphatic system. This may reflect the different binding properties of VEGFs to VEGFRs, in that VEGF-A binds to VEGFR-1 and -2, whereas VEGF-C acts through VEGFR-3, whose expression becomes restricted to lymphatics and certain veins during development. However, the finding that VEGF-C also binds to and activates VEGFR-2 may explain why it induces angiogenesis under certain conditions, which makes it relevant to experimental or clinical settings in which one would wish to block or to stimulate angiogenesis. In this paper we briefly discuss current knowledge on the biological activity of VEGF-C, emphasizing that, as has already been shown for a number of other angiogenic factors, the biological effects of VEGF-C are strictly dependent on the activity of other angiogenic regulators present in the microenvironment of the responding endothelial cells.
血管内皮生长因子(VEGF)-C是VEGF家族的新成员,VEGF家族是一组多肽生长因子,在心血管系统多个方面的生理和病理过程中发挥关键作用,包括血管生成、造血、血管生成和血管通透性。内皮细胞中的VEGF信号通过三种酪氨酸激酶受体(VEGFRs)发生,这些受体由内皮细胞和造血前体细胞表达。相对于最早描述的VEGF即VEGF-A而言,VEGF-A是一种内皮细胞特异性有丝分裂原和关键血管生成因子,VEGF-C似乎在淋巴系统发育中起主要作用。这可能反映了VEGFs与VEGFRs的不同结合特性,因为VEGF-A与VEGFR-1和-2结合,而VEGF-C通过VEGFR-3发挥作用,在发育过程中VEGFR-3的表达局限于淋巴管和某些静脉。然而,VEGF-C也能结合并激活VEGFR-2这一发现,或许可以解释为何它在某些条件下能诱导血管生成,这使得它与人们希望阻断或刺激血管生成的实验或临床环境相关。在本文中,我们简要讨论了目前关于VEGF-C生物学活性的知识,强调正如许多其他血管生成因子已被证明的那样,VEGF-C的生物学效应严格依赖于应答内皮细胞微环境中其他血管生成调节因子的活性。
Microsc Res Tech. 2001-10-15
Semin Thromb Hemost. 2000