Phosphatidylethanolamine at the Luminal Endothelial Surface-Implications for Hemostasis and Thrombotic Autoimmunity
Phosphatidylethanolamine at the Luminal Endothelial Surface-Implications for Hemostasis and Thrombotic Autoimmunity
复制标题
DOI：
10.1177/1076029609350620
复制
发表时间：
2011-04-01
影响因子：
2.9
通讯作者：
Zhao, Ming
中科院分区：
文献类型：
--
作者：
Li, Zhixin;Wells, Clive W.;Zhao, Ming
目标：越来越多的证据表明，磷脂酰乙醇胺（PE）是物理上存在于管腔内皮表面，在那里它暂时作为一个关键的抗凝剂。当前研究的目标有3个方面：表征PE在管腔内皮表面的分布特征;检查血栓形成患者抗PE（aPE）血清对血管内皮的免疫反应性;并讨论内皮细胞上调PE的潜在机制。方法：选择大鼠主动脉弓作为主要的交通血管，在显著的血流动力学负荷下。使用duramycin作为PE结合探针和免疫组织化学检查管腔内皮表面的PE和aPE血清的抗原谱的存在。使用经层流剪切应力或凝血酶处理的培养单层研究内皮细胞表面的磷脂酰乙醇胺上调。结果如下：在主动脉分流器、升主动脉和主动脉弓外曲的管腔内皮表面检测到高水平的PE。与患者血栓形成风险升高高度相关的aPE血清的抗原谱与PE沿内皮表面的分布沿着一致。最后，PE在培养的内皮细胞的表面响应于管腔剪切应力而不是凝血酶上调。结论：目前的数据描述了血管PE在血液内皮界面的物理分布。管腔PE表现出对抗PE自身免疫的脆弱性，并且与aPE和特发性血栓形成风险升高之间的相关性一致。
Objective: Accumulating evidence suggests that phosphatidylethanolamine (PE) is physically present at the luminal endothelial surface, where it tentatively functions as a critical anticoagulant. The goal of the current investigation was 3-fold: to characterize the distribution profile of PE at the luminal endothelial surface; to examine the immunoreactivity to the vascular endothelium by anti-PE (aPE) sera from patients presenting with thrombosis; and to discuss the potential mechanism of PE upregulation by endothelial cells. Methods: The rat aortic arch was selected as major conduit vessel under significant hemodynamic burden. The presence of PE and the antigenic profile of aPE sera at the luminal endothelial surface were examined using duramycin as a PE-binding probe and immunohistochemistry. Phosphatidylethanolamine upregulation at endothelial cell surface was investigated using cultured monolayer subject to laminar shear stress or thrombin treatment. Results: High levels of PE were detected at the luminal endothelial surface of aortic flow dividers, the ascending aorta, and the outer curvature of the aortic arch. The antigenic profiles of aPE sera, which are highly associated with elevated thrombotic risks in patients, are consistent with PE distribution along the endothelial surface. Finally, PE is upregulated at the surface of cultured endothelial cells in response to luminal shear stress but not thrombin. Conclusions: The current data describe the physical distribution of vascular PE at the blood-endothelium interface. The luminal PE presents a vulnerability to anti-PE autoimmunity and is consistent with the association between aPE and elevated risk for idiopathic thrombosis.