Milkiewicz Malgorzata, Ispanovic Eric, Doyle Jennifer L, Haas Tara L
School of Kinesiology and Health Sciences, York University, Toronto, Ont. M3J 1P3, Canada.
Int J Biochem Cell Biol. 2006 Mar;38(3):333-57. doi: 10.1016/j.biocel.2005.10.006. Epub 2005 Nov 7.
Angiogenesis provides a mechanism by which delivery of oxygen and nutrients is adapted to compliment changes in tissue mass or metabolic activity. However, maladaptive angiogenesis is integral to the process of several diseases common in Western countries, including tumor growth, vascular insufficiency, diabetic retinopathy and rheumatoid arthritis. Understanding the process of capillary growth, including the identification and functional analyses of key pro- and anti-angiogenic factors, provides knowledge that can be applied to improve/reverse these pathological states. Initially, angiogenesis research focused predominantly on vascular endothelial growth factor (VEGF) as a main player in the angiogenesis cascade. It is apparent now that participation of multiple angiogenic factors and signal pathways is critical to enable effective growth and maturation of nascent capillaries. The purpose of this review is to focus on recent progress in identifying angiogenesis signaling pathways that show promise as targets for successful induction or inhibition of capillary growth. The strategies applied to achieve these contradictory tasks are discussed within the framework of our existing fundamental knowledge of angiogenesis signaling cascades, with an emphasis on comparing the employment of distinctive tactics in modulation of these pathways. Innovative developments that are presented include: (1) inducing a pleiotropic response via activation or inhibition of angiogenic transcription factors; (2) modulation of nitric oxide tissue concentration; (3) manipulating the kallikrein-kinin system; (4) use of endothelial progenitor cells as a means to either directly contribute to capillary growth or to be used as a vehicle to deliver "suicide genes" to tumor tissue.
血管生成提供了一种机制，通过该机制氧气和营养物质的输送能够适应组织质量或代谢活动的变化。然而，适应性不良的血管生成是西方国家常见的几种疾病过程中不可或缺的一部分，包括肿瘤生长、血管功能不全、糖尿病视网膜病变和类风湿性关节炎。了解毛细血管生长过程，包括关键促血管生成因子和抗血管生成因子的鉴定及功能分析，可为改善/逆转这些病理状态提供知识。最初，血管生成研究主要聚焦于血管内皮生长因子（VEGF），认为它是血管生成级联反应中的主要参与者。现在很明显，多种血管生成因子和信号通路的参与对于新生毛细血管的有效生长和成熟至关重要。本综述的目的是关注在识别血管生成信号通路方面的最新进展，这些信号通路有望成为成功诱导或抑制毛细血管生长的靶点。在我们现有的血管生成信号级联基础知识框架内，讨论了为实现这些相互矛盾的任务所应用的策略，重点是比较在调节这些通路中采用的不同策略。介绍的创新性进展包括：（1）通过激活或抑制血管生成转录因子诱导多效性反应；（2）调节一氧化氮组织浓度；（3）操纵激肽释放酶 - 激肽系统；（4）使用内皮祖细胞作为直接促进毛细血管生长的手段，或用作将“自杀基因”递送至肿瘤组织的载体。
