Abstract 643: Impaired Integrin β3 Delays Endothelial Cell Regeneration and Contributes to Arteriovenous Graft Failure in mice

Objective: Neointima formation is associated with stenosis and subsequent thrombosis in arteriovenous grafts (AVG). A role of integrin β3 in the neointima formation of AVGs remains poorly understood. Approach and Results: In integrin β3-/- mice, we found significantly accelerated occlusion of AVGs compared to the wild type mice. This is caused by the development of neointima and lack of endothelial regeneration. The latter is a direct consequence of impaired functions of circulating angiogenic cells (CACs) and platelets in integrin β3-/- mice. Evidence suggests the involvement of platelet regulating CAC homing to and differentiation at graft sites via TGF-β1 and Notch signaling pathway. First, CACs deficient of integrin β3 impaired adhesion activity toward exposed subendothelium. Second, platelets from integrin β3-/- mice failed to sufficiently stimulate CACs to differentiate into mature endothelial cells. Finally, we found that TGF-β1 level was increased in platelets from integrin β3-/- mice and resulted...