Impaired Integrin β3 Delays Endothelial Cell Regeneration and Contributes to Arteriovenous Graft Failure in Mice. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Liang, Ming; Wang, Yun; Liang, Anlin; Dong, Jin-Fei; Du, Jie; Cheng, Jizhong
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 35:Issue 3(2015)
• Publication Date: 2015-03
• Subjects: arteriovenous graft -- circulating angiogenic cells -- integrin β3 -- neointima; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.114.305089
• Languages: English
• ISSNs: 1079-5642

Abstract

Abstract : Objective—: Neointima formation is associated with stenosis and subsequent thrombosis in arteriovenous grafts (AVGs). 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 with 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 transforming growth factor-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 transforming growth factor-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 transforming growth factor-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 wild-type mice. Conclusions—: Our results suggest that boosting integrin β3 function in the endothelial cells and platelets could prevent neointima and thrombosis in AVGs. Abstract : Supplemental Digital Content is available in the text.