Growth control and morphogenesis in the development and pathology of arteries

Abstract

We briefly review and compare the current knowledge of growth mechanisms for the mitogenic response of endothelial cells and smooth-muscle cells to injury. For the endothelium, this focuses on the evidence that growth control involves two components: an endogenous inhibition mechanism, which can be overcome either by fibroblast growth factor (FGF) or by other agents that disrupt cell-cell junctions, and a separate mechanism, which requires FGF to allow cells to respond to a mitogenic effect. The smooth-muscle cell story is more complex; however, there is evidence here as well of an endogenous inhibitory mechanism, which may be overcome by a wide variety of agents. Platelet-derived growth factor, long seen as a major mitogen, does not itself now appear to be a major mitogen in vivo. In contrast, FGF also seems to play a major role in initiating smooth-muscle replication. Other molecules, including angiotensin II, bradykinin, thrombin, and catecholamines, are beginning to appear to play major roles in control of smooth-muscle replication in vivo as well.