Role of transforming growth factor beta in angiogenesis

Abstract

Transforming growth factor beta (TGFß) is a pleiotropic factor that plays pivotal roles in both vasculogenesis and angiogenesis and thus is indispensable for development and homeostasis of the vascular system. TGFß drives vascular responses via its binding to a TGFß receptor complex formed by type I and type II receptors, as well as type III co-receptors present on both endothelial and mural cells. Signaling by these receptors is context-dependent and tightly regulated, particularly on cultured endothelial cells, where TGFß can either promote or suppress endothelial migration, proliferation, permeability, and sprouting. These, together with evidence obtained from knockout animals for different TGFß receptor types, and genetic studies in humans linking mutations in TGFß signaling components to cardiovascular syndromes, suggest that TGFß is a central mediator of angiogenesis, where it may play contrasting roles depending on the stage of the process. This review presents an overview of knowledge accumulated to date on TGFß's role in angiogenesis as well as vascular biology and vascular disease and discusses potential applications of this knowledge to the treatment of angiogenesis-dependent diseases such as cancer.