Patterning the Artery Wall by Lateral Induction of Notch Signaling

Abstract

Blood vessels exhibit a common structure composed of layers of cells encircling a central lumen. Arteries generally have more layers than veins have, and different arteries in the same individual can have different numbers of layers. Because all blood vessels are built around a monolayer of endothelial cells, the variation in wall structure is due to variable numbers of smooth muscle-containing layers in the tunica media. Indeed, Wolinsky and Glagov's classic article showed that the relation between lumen diameter and wall thickness across a wide range of mammalian species is a function of the number of layers of smooth muscle and elastic fibers that are present in the arterial media.1 Yet precisely how layers of smooth muscle are formed during vascular development and what molecular mechanisms operate to produce different numbers of layers in different blood vessels is still poorly understood. Article see p 314 For many years the prevailing hypothesis has been that wall thickness is determined by wall tension, and the number of layers found in a given blood vessel is that number sufficient to normalize wall tension to values (dynes/cm2) within a narrow physiological range per layer.2 The advent of transgenic mouse technology generated new animal models that provided for interesting tests of the accepted paradigms for the development of vessel wall structure. For example, mice expressing a growth hormone transgene driven by a metallothionein promoter (MtGH) reached a body mass 1.8-fold that of wild-type littermate mice.3 Most of the internal organs in these mice exhibited proportional increases in mass in comparison with wild-type littermates (eg, kidney=1.9-fold; heart= 1.8-fold).4 To accommodate the increases in blood flow required to support these larger bodies, the aortas of transgenic MtGH mice exhibited a number of structural changes. For example, aortic lumen diameter was increased (1.22-fold), …