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腔内皮细胞表面的磷脂酰乙醇胺--对止血和血栓性自身免疫的影响。

Phosphatidylethanolamine at the luminal endothelial surface--implications for hemostasis and thrombotic autoimmunity.

机构信息

Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

出版信息

Clin Appl Thromb Hemost. 2011 Apr;17(2):158-63. doi: 10.1177/1076029609350620. Epub 2009 Nov 10.

DOI:10.1177/1076029609350620
PMID:19903695
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3866907/
Abstract

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 PEbinding 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.

摘要

目的

越来越多的证据表明,磷脂酰乙醇胺(PE)存在于腔内皮细胞表面的管腔侧,在那里它暂时作为一种关键的抗凝剂发挥作用。本研究的目的有三个:一是描述 PE 在腔内皮细胞表面的分布特征;二是通过抗-PE(aPE)血清检查血栓形成患者血管内皮的免疫反应;三是讨论内皮细胞上调 PE 的潜在机制。

方法

选择大鼠主动脉弓作为在显著血流动力学负荷下的主要导管血管。使用 duramycin 作为 PE 结合探针和免疫组织化学,检查 PE 的存在和 aPE 血清在腔内皮表面的抗原特征。通过层流剪切力或凝血酶处理培养的单层来研究内皮细胞表面的 PE 上调。

结果

在主动脉分流器、升主动脉和主动脉弓的外曲处的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 血清的抗原谱与沿内皮表面的 PE 分布一致。最后,PE 在响应腔剪切力而不是凝血酶时在上皮细胞表面上调。

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。腔侧的 PE 容易受到抗-PE 自身免疫的影响,并且与 aPE 和特发性血栓形成风险升高之间存在关联。

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