Molecular Control of Vascular Tube Morphogenesis and Stabilization: Regulation by Extracellular Matrix, Matrix Metalloproteinases, and Endothelial Cell–Pericyte Interactions

Abstract

that are delivered. There is considerable evidence that ECM can provide both stimulatory and inhibitory signals [24, 26], and thus, the ECM composition, the vascular cell types, and the biological context of the signaling dictate the cellular response that occurs. An important regulator of ECM structure and function are MMPs, which can not only degrade matrix components [25, 26, 41, 46] but can also release liberate factors such as cytokines from these matrices to affect vascular cell behavior. Within the vascular wall, homotypic interactions between ECs [31] and heterotypic interactions of ECs and mural cells affect ECM production and deposi-tion, [81] as well as its ability to be degraded by MMPs [77]. Many new studies are now focused on such interactions to understand how mural cells affect EC behavior during development and under various disease conditions [1, 5, 42, 50, 81]. In this chapter, we review past and present work that addresses mechanisms by which ECM, MMPs, and EC-pericyte interactions influence vascular tube assembly and remodeling, tube stabilization, and vascular regression to control tissue vasculariza-tion in normal versus disease states.