Growth arrest-specific gene 6 expression in proliferating rabbit vascular smooth muscle cells in vitro and in vivo

Proliferation and migration of vascular smooth muscle cells (VSMCs) are inv olved in the processes of atherosclerosis and restenosis. The protein produ ct of the growth arrest-specific gene 6 (Gas-6) has recently been identifie d as a ligand for the Axl/Rse/ Mer tyrosine kinase receptor family, which m ay be involved in proliferation and migration of VSMCs. Here we show that G as-6 gene expression is increased in proliferating VSMCs in tissue culture (2.5-fold increase by Northern blot) and following neointimal proliferation in a rabbit balloon-injury model (3-fold increase by Western blot). Neithe r platelet-derived growth factor (PDGF) nor thrombin stimulate the expressi on of Gas-6 in cultured VSMCs despite the ability of the PDGF, but not thro mbin, to stimulate proliferation in growth-arrested cells. These data sugge st a role for the Gas-6 regulatory system in VSMC proliferation, which may be a target for therapeutic interventions in the atherosclerotic process an d restenosis after angioplasty.