Objectives—Bone marrow (BM)-derived endothelial progenitor cells (EPCs) and vascular smooth muscle progenitor cells (VPCs) contribute to neointima formation, whereas the angiotensin II (Ang II) type 1 receptor (AT₁)-mediated action on BM-derived progenitors remains undefined.

Methods and Results—A wire-induced vascular injury was performed in the femoral artery of BM-chimeric mice whose BM was repopulated with AT₁-deficient (BM-Agtr1^-/-) or wild-type (BM-Agtr1^+/+) cells. Neointima formation was profoundly reduced by 38% in BM-Agtr1^-/- mice. Although the number of circulating EPCs (Sca-1⁺Flk-1⁺) and extent of reendothelialization did not differ between the 2 groups, the numbers of both circulating VPCs (c-Kit^-Sca-1⁺Lin^-) and tissue VPCs (Sca-1⁺CD31^-) incorporated into neointima were markedly decreased in BM-Agtr1^-/- mice. The accumulation of aggregated platelets and their content of stromal cell–derived factor-1 (SDF-1) were significantly reduced in BM-Agtr1^-/- mice, accompanied by a decrease in the serum level of SDF-1. Thrombin-induced platelets aggregation was dose-dependently inhibited (45% at 0.1 IU/mL, P<0.05) in Agtr1^-/- platelets compared with Agtr1^+/+ platelets, accompanied by the reduced expression and release of SDF-1.

Conclusions—The BM-AT₁ receptor promotes neointima formation by regulating the mobilization and homing of BM-derived VPCs in a platelet-derived SDF-1–dependent manner without affecting EPC-mediated reendothelialization.