Abstract 213: Deletion of Epha2 Reduces Fibroproliferative Remodeling in Atherosclerosis and Vascular Smooth Muscle

Advanced atherosclerosis involves the recruitment of vascular smooth muscle cells, leading to smooth muscle-mediated fibroproliferative remodeling and plaque stiffening. We previously demonstrated the neuronal guidance receptor EphA2 shows enhanced expression in murine and human atherosclerosis, and EphA2 deletion in atherosclerosis-prone ApoE knockout mice attenuates lesion formation and endothelial cell activation in models of atherosclerosis. We now demonstrate deletion of EphA2 attenuates plaque progression to advanced stages associated with diminished smooth muscle content. While contractile smooth muscle cells show minimal EphA2 expression in vitro and in vivo, transition to the synthetic phenotype results in enhanced EphA2 expression and luciferase reporter activity in vitro and in atherosclerotic lesions. Furthermore, forced expression of EphA2 in quiescent smooth muscle cells is sufficient to suppress contractile smooth muscle markers, suggesting a role for EphA2 in smooth muscle phenotypic switc...