Intracellular signaling in arterial smooth muscle migration versus proliferation

Directed migration and proliferation of arterial smooth muscle cells are key events in the formation and development of atherosclerotic lesions and in restenosis following angioplasty. Both directed migration and proliferation are regulated by polypeptides induced following injury in the arterial wall or derived from circulating cells. Migration and proliferation can be stimulated by the same polypeptide through a common receptor This is the case with platelet-derived growth factor (PDGF), which is the strongest known growth factor and chemoattractant for smooth muscle cells. The PDGF-induced signal transduction pathways leading to directed migration are not identical to those leading to proliferation. Thus, increased phosphatidylinositol turnover and calcium mobilization are associated with directed migration of smooth muscle cells, whereas activation of the mitogen-activated protein (MAP) kinase cascade, activation of translation and the p70 S6 kinase, and regulation of the cyclin-dependent kinases can regulate DNA replication and proliferation. Engagement of distinct signal transduction pathways may determine when a smooth muscle cell migrates and when it resides to proliferate in response to a vascular injury.