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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. © 2023 by the Society for Vascular Surgery. Published by Elsevier Inc.


John T Langford, Luis Gonzalez, Ryosuke Taniguchi, Anand Brahmandam, Weichang Zhang, Alan Dardik. EphB4 monomer inhibits chronic graft vasculopathy in an aortic transplant model. JVS-vascular science. 2023;4:100109

PMID: 37519335

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