The mechanics of vascular cell motility

Alterations in vascular cell shape and motility occur during developmental processes and in response to injury. Similarly, during tumor vascularizatio n and atherogenesis, endothelial and smooth muscle cells undergo motile and proliferative responses to extracellular cues. Recent inroads into our und erstanding of signal transduction have identified several candidate pathway s by which the extracellullar matrix- and growth factor-mediated stimulatio n of vascular cell motility ma! Le mediated. The multiple and divergent ext racellular stimuli thar stimulate vascular motile responses may converge on the cytoskeleton via a family of ras-related GTPases. Biochemical analyses as well as examination of cytoskeletal dynamics in vivo indicate that acti n polymerization at the forward aspects of spreading cytoplasm is capable o f driving forward protrusion formation in the absence of a conventional act in motor. Actin polymerization at the plasma membrane of leading lamellae m ay be mediated both by de novo nucleation of actin filaments and the genera tion of free filament ends by uncapping the barbed ends of existing actin f ilaments. This review summarizes the most recent findings in extracellular- cytoskeletal-signal transduction, therein, providing a framework to explain the remarkable remodeling seen in the vasculature during developmental and disease-related processes.