FSP-1 Silencing in Bone Marrow Cells Suppresses Neointima Formation in Vein Graft

Rationale:Fibroblast-specific protein 1 (FSP-1) plays multiple roles in promoting cell proliferation and motility. Increased FSP-1 expression in smooth muscle cells (SMCs) has been associated with their enhanced proliferation. 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-1 promoter). 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 BM-derived cells expressing the SDF-1α receptor CXCR4; homing of FSP-1–positive cells was found to be dependent on platelet-derived SDF-1α. FSP-1 was expressed in 8% of the BM cells, and 20% of these express CD45; 85% of FSP-1–positive cells...