Karamysheva A F
Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia.
Biochemistry (Mosc). 2008 Jul;73(7):751-62. doi: 10.1134/s0006297908070031.
Tissue activity of angiogenesis depends on the balance of many stimulating or inhibiting factors. The key signaling system that regulates proliferation and migration of endothelial cells forming the basis of any vessel are vascular endothelium growth factors (VEGF) and their receptors. The VEGF-dependent signaling system is necessary for formation of the embryonic vascular system. Neoangiogenesis during tumor growth is also associated with activation of this signaling system. The biological significance of the effect of such system on the cells depends on the content in tissue of various factors of the VEGF family and their receptors, while in the case of VEGFA it is defined by the ratio of different isoforms of this growth factor. A number of other signaling systems are also involved in regulation of the main steps of vessel formation. The signaling system Dll4/Notch regulates selection of endothelial cells for beginning of angiogenic expansion by endowing particular properties to endothelial cells leading in this process. An important step in vessel stabilization and maturation is vascular wall formation. Signaling system PDGFB/PDGFRbeta as well as angiopoietins Ang1, Ang2, and their receptor Tie2 are involved in recruiting mural cells (pericytes and smooth muscle cells). Identification of key molecules involved in the regulation of angiogenesis may provide new possibilities for development of drugs suitable for inhibition of angiogenesis or its stimulation in various pathologies.
血管生成的组织活性取决于多种刺激或抑制因子之间的平衡。调节构成任何血管基础的内皮细胞增殖和迁移的关键信号系统是血管内皮生长因子（VEGF）及其受体。VEGF依赖的信号系统对于胚胎血管系统的形成是必需的。肿瘤生长过程中的新生血管生成也与该信号系统的激活有关。该系统对细胞作用的生物学意义取决于VEGF家族各种因子及其受体在组织中的含量，而就VEGFA而言，它由该生长因子不同异构体的比例决定。许多其他信号系统也参与血管形成主要步骤的调节。信号系统Dll4/Notch通过赋予在此过程中起主导作用的内皮细胞特定特性来调节用于启动血管生成扩张的内皮细胞的选择。血管壁形成是血管稳定和成熟的一个重要步骤。信号系统PDGFB/PDGFRβ以及血管生成素Ang1、Ang2及其受体Tie2参与募集壁细胞（周细胞和平滑肌细胞）。鉴定参与血管生成调节的关键分子可能为开发适用于抑制或刺激各种病理状态下血管生成的药物提供新的可能性。
