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

Abstract
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 in enhanced Notch1 activation in CACs in AVGs. These results demonstrate that integrin β3 is critical for endothelial cell homing and differentiation. The increased TGF-β1 and Notch1 signaling mediates integrin β3-/--induced AVG occlusion. This accelerated occlusion of AVGs was reversed in integrin β3-/- mice transplanted with the bone marrow from WT mice.
Conclusion: Our results suggest that boosting integrin β3 function in the endothelial cells and platelets could prevent neointima and thrombosis in AVGs.
Author Disclosures: M. Liang: None. A. Liang: None. Y. Wang: None. J. Dong: None. J. Du: None. J. Cheng: None.
This research has received full or partial funding support from the American Heart Association.
- © 2015 by American Heart Association, Inc.
This Issue
Jump to
Article Tools
- Abstract 643: Impaired Integrin β3 Delays Endothelial Cell Regeneration and Contributes to Arteriovenous Graft Failure in miceMing Liang, Anlin Liang, Yun Wang, Jin-fei Dong, Ji Du and Jizhong ChengArteriosclerosis, Thrombosis, and Vascular Biology. 2015;35:A643, originally published August 11, 2015
Citation Manager Formats
Share this Article
- Abstract 643: Impaired Integrin β3 Delays Endothelial Cell Regeneration and Contributes to Arteriovenous Graft Failure in miceMing Liang, Anlin Liang, Yun Wang, Jin-fei Dong, Ji Du and Jizhong ChengArteriosclerosis, Thrombosis, and Vascular Biology. 2015;35:A643, originally published August 11, 2015