| First Author | Liang M | Year | 2015 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 35 |
| Issue | 3 | Pages | 607-15 |
| PubMed ID | 25614287 | Mgi Jnum | J:241195 |
| Mgi Id | MGI:5897969 | Doi | 10.1161/ATVBAHA.114.305089 |
| Citation | Liang M, et al. (2015) Impaired integrin beta3 delays endothelial cell regeneration and contributes to arteriovenous graft failure in mice. Arterioscler Thromb Vasc Biol 35(3):607-15 |
| abstractText | OBJECTIVE: Neointima formation is associated with stenosis and subsequent thrombosis in arteriovenous grafts (AVGs). A role of integrin beta3 in the neointima formation of AVGs remains poorly understood. APPROACH AND RESULTS: In integrin beta3(-/-) 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 beta3(-/-) mice. Evidence suggests the involvement of platelet regulating CAC homing to and differentiation at graft sites via transforming growth factor-beta1 and Notch signaling pathway. First, CACs deficient of integrin beta3 impaired adhesion activity toward exposed subendothelium. Second, platelets from integrin beta3(-/-) mice failed to sufficiently stimulate CACs to differentiate into mature endothelial cells. Finally, we found that transforming growth factor-beta1 level was increased in platelets from integrin beta3(-/-) mice and resulted in enhanced Notch1 activation in CACs in AVGs. These results demonstrate that integrin beta3 is critical for endothelial cell homing and differentiation. The increased transforming growth factor-beta1 and Notch1 signaling mediates integrin beta3(-/-)-induced AVG occlusion. This accelerated occlusion of AVGs was reversed in integrin beta3(-/-) mice transplanted with the bone marrow from wild-type mice. CONCLUSIONS: Our results suggest that boosting integrin beta3 function in the endothelial cells and platelets could prevent neointima and thrombosis in AVGs. |
