EphB4 monomer inhibits chronic graft vasculopathy in an aortic transplant model

T cells and macrophages play an important role in the formation of allograft vasculopathy, which is the predominant form of chronic rejection in cardiac transplants. Arteries express Ephrin-B2 as a marker of arterial identity, whereas circulating monocytes express the cognate receptor EphB4, which f...

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Bibliographic Details
Published in:JVS-vascular science 2023-01, Vol.4, p.100109-100109, Article 100109
Main Authors: Langford, John T., Gonzalez, Luis, Taniguchi, Ryosuke, Brahmandam, Anand, Zhang, Weichang, Dardik, Alan
Format: Article
Language:English
Subjects:
Allograft
Allograft vasculopathy
Eph-B4
Ephrin-B2
Neointimal hyperplasia
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Summary:T cells and macrophages play an important role in the formation of allograft vasculopathy, which is the predominant form of chronic rejection in cardiac transplants. Arteries express Ephrin-B2 as a marker of arterial identity, whereas circulating monocytes express the cognate receptor EphB4, which facilitates monocyte adhesion to the endothelial surface. Adherent monocytes transmigrate and differentiate into macrophages that activate T cells and are a main source of tissue damage during rejection. We hypothesized that inhibition of Ephrin-B2-EphB4 binding would decrease immune cell accumulation within a transplanted graft and prevent allograft vasculopathy. We used EphB4 monomer to inhibit Ephrin-B2-EphB4 binding in a rat infrarenal aortic transplant model. Rats treated with EphB4 monomer had fewer macrophages and T cells in the aortic allografts at 28 days, as well as significantly less neointima formation. These data show that the Ephin-B2-EphB4 axis may be an important target for prevention or treatment of allograft vasculopathy.
ISSN:2666-3503
2666-3503
DOI:10.1016/j.jvssci.2023.100109