H-RAS Controls Phenotypic Profiles of Vascular Smooth Muscle Cells and the Pathogenesis of Vascular Proliferative Disorders

Vascular smooth muscle (VSMC) migration, prolifera-tion, and hypertrophy following physical, chemical, or biological injury are key events in the onset and progression of vascular proliferative disorders, such as atherosclerosis, postangioplasty stenosis, venous bypass graft failure, and transplantation. Under normal conditions, VSMCs exist in a quiescent state of growth that supports contractile function and structural and functional integrity of the vascular wall. Vascular injury disrupts critical cell–cell and cell–matrix interactions, leading to activation of VSMCs. The activated VSMC phenotype is characterized by gradual loss of differ-entiated characteristics, increased response to chemotactic agents, and uncontrolled proliferation. Not surprisingly, the quest for molecular triggers of VSMC proliferation led investigators to studies of cell cycle control proteins and mitogenic signaling within the vascular wall. Of note are