Plasma Phospholipid Transfer Protein Promotes Platelet Aggregation.
Plasma Phospholipid Transfer Protein Promotes Platelet Aggregation.
复制标题
血浆磷脂转移蛋白促进血小板聚集。
DOI：
10.1055/s-0038-1675228
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发表时间：
2018-12
影响因子：
6.7
通讯作者：
Jiang XC
中科院分区：
文献类型：
--
作者：
Zhao XM;Wang Y;Yu Y;Jiang H;Babinska A;Chen XY;He KG;Min XD;Han JJ;Yang CX;Deng K;Xue J;Zhang X;Song GH;Qin SC;Jiang XC
目前尚不清楚血浆磷脂转移蛋白（PLTP）与血液高凝或低凝状态是否相关。本研究旨在探究PLTP对血小板聚集的直接影响及其潜在机制。研究分离了人或小鼠的洗涤血小板、小鼠富含血小板血浆以及人重组PLTP。研究发现人血小板中存在PLTP。我们评估了二磷酸腺苷（ADP）、胶原蛋白和凝血酶诱导的血小板聚集、磷脂酰丝氨酸外翻，以及光血栓诱导的小鼠脑梗死情况。PLTP过表达会增强血小板聚集，而PLTP缺乏则产生相反的效果。人重组PLTP以剂量依赖的方式增强了小鼠和人血小板的聚集。磷脂酰丝氨酸外翻为凝血因子的相互作用提供了水/脂界面，从而加速血栓形成。与野生型对照组相比，PLTP转基因小鼠的血小板质膜外表面磷脂酰丝氨酸显著增多，而PLTP缺陷型小鼠的血小板表面磷脂酰丝氨酸则显著减少，因此PLTP会影响纤维蛋白原与质膜的结合。此外，重组PLTP与ADP共同作用，显著增加了PLTP缺陷型血小板质膜上磷脂酰丝氨酸的暴露，进而增加了纤维蛋白原的结合。PLTP过表达显著加快了光血栓诱导的小鼠脑梗死发生率，而PLTP缺乏则显著降低了梗死发生频率。我们得出结论，PLTP促进血小板质膜上磷脂酰丝氨酸外翻，并加速ADP或胶原蛋白诱导的血小板聚集。这种作用在剪切应力条件下对凝血酶生成和血小板聚集的起始过程起着重要作用。因此，PLTP参与了血液高凝过程。所以，抑制PLTP可能是一种对抗血栓形成的新方法。
It remains unclear whether plasma phospholipid transfer protein (PLTP) is involved in hypercoagulation or hypocoagulation. This study investigated the direct effect of PLTP on platelet aggregation and the underlying mechanism. Washed platelets from humans or mice and mouse platelet–rich plasma and human recombinant PLTP were isolated. PLTP is present in human platelets. We assessed ADP-, collagen-, and thrombin-induced platelet aggregation, phosphatidylserine externalization, and photothrombosis-induced cerebral infarction in mice. PLTP overexpression increased platelet aggregation, while PLTP deficiency had the opposing reaction. Human recombinant PLTP increased both mouse and human platelet aggregation in a dose-dependent manner. Phosphatidylserine externalization provides a water/lipid surface for the interaction of coagulation factors, which accelerates thrombosis. Compared with wild type controls, platelets from PLTP transgenic mice had significantly more phosphatidylserine on the exterior surface of the plasma membrane, whereas platelets from PLTP-deficient mice had significantly less on the surface, thus PLTP influences fibrinogen binding on the plasma membrane. Moreover, recombinant PLTP together with ADP significantly increased phosphatidylserine exposure on the plasma membrane of PLTP-deficient platelets, thereby increasing fibrinogen binding. PLTP overexpression significantly accelerated the incidence of photothrombosis-induced infarction in mice, whereas PLTP deficiency significantly reduced the frequency of infarction. We concluded that PLTP promotes phosphatidylserine externalization at the plasma membrane of platelets and accelerates ADP- or collagen-induced platelet aggregation. This effect plays an important role in the initiation of thrombin generation and platelet aggregation under sheer stress conditions. Thus, PLTP is involved in hypercoagulation. Therefore, PLTP inhibition could be a novel approach for countering thrombosis.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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