Objective To study how FSP—1 contributes to neointima formation of vein grafts.Methods Arteriovenous grafts were created in wild—type or FSP—1-GFP mice (green fluorescent protein expression regulated by FSP—1promoter).The effects of FSP—1 on bone marrow (BM) cell migration and on SMC proliferation were studied in vivo and in vitro.Results On creation of a vein graft,there was rapid deposition of platelets on the denuded surface leading to secretion of the chemokine stromal cell-derived factor—1α (SDF—1α).This was followed by recruitment of BMderived cells expressing the SDF—1α receptor CXCR4;homing of FSPl-positive cells was found to be dependent on plateletderived SDF—1α.FSP—1 was expressed in 8% of the BM cells,and 20 % of these express CD45; 85% of FSP—l-positive cells express CD11b.We found that the FSP—l-positive cells migrated into the vein graft in a Rac—1-dependent fashion.FSP1 expression was also found to stimulate proliferation of SMCs through a MEKSERK5 signaling pathway that can be suppressed by a dominantnegative Racl.Consequently,knocking down FSP1 expression in BM cells prevented neointimal formation.