Department of Chemical and Biomolecular Engineering, Lafayette College, Easton, Pennsylvania, USA.
Tissue Eng Part B Rev. 2010 Jun;16(3):361-70. doi: 10.1089/ten.TEB.2009.0611.
Microvascular remodeling is a complex process that includes many cell types and molecular signals. Despite a continued growth in the understanding of signaling pathways involved in the formation and maturation of new blood vessels, approximately half of all compounds entering clinical trials will fail, resulting in the loss of much time, money, and resources. Most pro-angiogenic clinical trials to date have focused on increasing neovascularization via the delivery of a single growth factor or gene. Alternatively, a focus on the concerted regulation of whole networks of genes may lead to greater insight into the underlying physiology since the coordinated response is greater than the sum of its parts. Systems biology offers a comprehensive network view of the processes of angiogenesis and arteriogenesis that might enable the prediction of drug targets and whether or not activation of the targets elicits the desired outcome. Systems biology integrates complex biological data from a variety of experimental sources (-omics) and analyzes how the interactions of the system components can give rise to the function and behavior of that system. This review focuses on how systems biology approaches have been applied to microvascular growth and remodeling, and how network analysis tools can be utilized to aid novel pro-angiogenic drug discovery.
微血管重构是一个复杂的过程，包括许多细胞类型和分子信号。尽管人们对参与新血管形成和成熟的信号通路的理解不断深入，但大约一半进入临床试验的化合物都会失败，从而导致大量时间、金钱和资源的损失。迄今为止，大多数促血管生成的临床试验都集中在通过单一生长因子或基因的传递来增加新血管生成。或者，关注整个基因网络的协同调节可能会更深入地了解潜在的生理学，因为协调的反应大于其各部分的总和。系统生物学提供了一个全面的血管生成和血管生成的网络视图，这可能使我们能够预测药物靶点，以及激活这些靶点是否会产生预期的结果。系统生物学整合了来自各种实验源的复杂生物数据（组学），并分析系统组件的相互作用如何产生该系统的功能和行为。这篇综述重点介绍了系统生物学方法如何应用于微血管生长和重塑，以及网络分析工具如何用于帮助新的促血管生成药物发现。
