GROWTH-CONTROL AND MORPHOGENESIS IN THE DEVELOPMENT AND PATHOLOGY OF ARTERIES

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.