Role of Transforming Growth Factor Beta Family in Angiogenesis

Abstract

Transforming growth factor-beta (TGF beta) 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. TGF beta drives vascular responses via its binding to a TGF beta receptor complex formed by type I and type II receptors, as well a 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 TGF beta can either promote or suppress endothelial migration, proliferation, permeability and sprouting. These, together with evidence obtained from knock-out animals for different TGF beta receptor types, and genetic studies in humans linking mutations in TGF beta signaling components to cardiovascular syndromes, suggest that TGF beta 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 TGF beta'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.