Improving the Outcome of Vein Grafts: Should Vascular Surgeons Turn Veins into Arteries?
Improving the Outcome of Vein Grafts: Should Vascular Surgeons Turn Veins into Arteries?
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DOI：
10.3400/avd.ra.17-00008
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发表时间：
2017-03-24
影响因子：
0.8
通讯作者：
Dardik A
中科院分区：
文献类型：
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作者：
Isaji T;Hashimoto T;Yamamoto K;Santana JM;Yatsula B;Hu H;Bai H;Jianming G;Kudze T;Nishibe T;Dardik A
自体静脉移植物仍然是动脉搭桥术的金标准管道，特别是用于治疗严重肢体缺血。静脉移植物适应动脉环境，即，充分的扩张和壁增厚有助于静脉移植物的上级性能。然而，异常的静脉壁重塑和过度的新生内膜增生通常会导致静脉移植失败。由于PREVENT试验未能改善静脉移植物的结局，新的策略集中在静脉内皮细胞对术后动脉环境的适应性反应上。Eph-B4是胚胎发育过程中静脉内皮的决定因素，在成年静脉组织中仍有表达和功能。手术后，静脉移植物失去其静脉身份，Eph-B4表达丧失;然而，动脉身份没有获得，与所有血管身份的丧失一致。在小鼠静脉移植物中，静脉Eph-B4信号传导的刺激促进内皮细胞中静脉身份的保留，并且与不增厚的静脉移植物壁相关。Eph-B4调节与血管生物学相关的下游信号通路，包括小窝蛋白-1、Akt和内皮型一氧化氮合酶（eNOS）。Eph-B4信号通路的调节可能是预防静脉移植失败的新的治疗靶点。
Autogenous vein grafts remain the gold standard conduit for arterial bypass, particularly for the treatment of critical limb ischemia. Vein graft adaptation to the arterial environment, i.e., adequate dilation and wall thickening, contributes to the superior performance of vein grafts. However, abnormal venous wall remodeling with excessive neointimal hyperplasia commonly causes vein graft failure. Since the PREVENT trials failed to improve vein graft outcomes, new strategies focus on the adaptive response of the venous endothelial cells to the post-surgical arterial environment. Eph-B4, the determinant of venous endothelium during embryonic development, remains expressed and functional in adult venous tissue. After surgery, vein grafts lose their venous identity, with loss of Eph-B4 expression; however, arterial identity is not gained, consistent with loss of all vessel identity. In mouse vein grafts, stimulation of venous Eph-B4 signaling promotes retention of venous identity in endothelial cells and is associated with vein graft walls that are not thickened. Eph-B4 regulates downstream signaling pathways of relevance to vascular biology, including caveolin-1, Akt, and endothelial nitric oxide synthase (eNOS). Regulation of the Eph-B4 signaling pathway may be a novel therapeutic target to prevent vein graft failure.