EphB4 monomer inhibits chronic graft vasculopathy in an aortic transplant model.
EphB4 monomer inhibits chronic graft vasculopathy in an aortic transplant model.
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DOI：
10.1016/j.jvssci.2023.100109
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Dardik, Alan
中科院分区：
文献类型：
--
作者：
Langford, John T;Gonzalez, Luis;Taniguchi, Ryosuke;Brahmandam, Anand;Zhang, Weichang;Dardik, Alan
T细胞和巨噬细胞在心脏移植慢性排斥反应的主要形式--移植物血管病变的形成中起着重要作用。动脉表达EPhin-B2作为动脉识别的标志，而循环中的单核细胞表达同源受体EphB4，这有助于单核细胞与内皮细胞表面的黏附。黏附的单核细胞迁移和分化为巨噬细胞，激活T细胞，是排斥反应中组织损伤的主要来源。我们假设，抑制EPhin-B2-EphB4结合将减少移植移植物内免疫细胞的聚集，并防止同种异体移植物血管病变。在大鼠肾下动脉移植模型中，我们使用EphB4单体抑制EPhin-B2-EphB4的结合。28天后，接受EphB4单体治疗的大鼠移植主动脉中巨噬细胞和T细胞减少，新生内膜形成明显减少。这些数据表明，Ephin-B2-EphB4轴可能是预防或治疗移植物血管病变的重要靶点。
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.