Building a Vessel Wall With Notch Signaling

Abstract

See related article, pages 466–475 Blood vessel walls are built and maintained by 2 interdependent cell types, endothelial cells and mural cells. Signals exchanged between these 2 cell types control the formation, maturation, remodeling, and function of microvascular networks. Mural cells are either pericytes in the microvasculature or smooth muscle cells (SMCs) in larger vessels. Interactions between endothelial cells and mural cells serve to stabilize nascent capillary vessels, provide endothelial cell survival factors, inhibit endothelial cell proliferation, promote mural cell differentiation, and guide vascular network remodeling.1,2 Yet precisely how endothelial cells recruit mural cells to form a functional vessel wall is still incompletely understood. The initial steps in this process of vessel wall formation, called investment, involve the establishment of cell-cell contacts between endothelium and incoming mural cells, which triggers a self-reinforcing mechanism to maintain the contacts and initiate the next phase of vessel wall maturation. N-cadherin appears to be important for heterotypic cell-cell adhesion between endothelial cells and nascent SMCs in the embryonic day 12.5 dorsal aorta.3 As vascular development proceeds, an iterative investment sequence is set into motion, as is evident by the multilayered structure of the tunica media that is produced in large vessels. In the microvasculature, communication between endothelial cells and mural cells prevents vascular regression and promotes maturation processes in both cell types.2 Investment of microvessels with pericytes is a reversible process that is highly responsive to changes in the rate and direction of blood flow.4 Although these basic steps of vessel wall investment have been known for many years, the molecular mechanisms that are responsible for morphogenesis of this structure are still not well understood. In this issue of Circulation Research , a report by Liu et al begins to identify some of the key early players in this …