Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability.

Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability.
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血小板因子ⅩⅢ - A调节血小板功能,促进血块回缩及稳定性。

DOI:
10.1016/j.rpth.2023.100200
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发表时间:
2023-07
影响因子:
4.6
通讯作者:
Jones, Christopher I.
Jones, Christopher I.
中科院分区:
医学2区
文献类型:
--
作者:
Mitchell, Joanne L.;Little, Gemma;Bye, Alexander P.;Gaspar, Renato S.;Unsworth, Amanda J.;Kriek, Neline;Sage, Tanya;Stainer, Alexander;Sangowawa, Ibidayo;Morrow, Gael B.;Bastos, Ricardo N.;Shapiro, Susan;Desborough, Michael J. R.;Curry, Nicola;Gibbins, Jonathan M.;Whyte, Claire S.;Mutch, Nicola J.;Jones, Christopher I.

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凝血因子XIII(FXIII)是止血系统中重要的酶原。血浆衍生酶激活的FXIII交联血栓内的纤维蛋白纤维以增加其机械强度,并将纤维蛋白与纤维蛋白溶解抑制剂(特别是α2-抗纤溶酶)交联以增加对纤维蛋白溶解的抵抗力。我们先前已经表明,细胞FXIII(因子XIII-A [FXIII-A]),这是丰富的血小板细胞质中,是外化到活化的膜和交联细胞外基质。细胞FXIII-A对血小板活化和血小板功能的贡献尚未得到广泛研究。本研究旨在确定血小板FXIII-A在血小板功能中的作用。我们在一系列血小板功能和凝血试验中使用了具有细胞渗透性FXIII抑制剂的正常健康血小板和来自FXIII缺乏患者的血小板作为无FXIII血小板模型。我们的数据表明,血小板FXIII-A在激动剂刺激后增强纤维蛋白原与血小板表面的结合,并在全血血栓形成测定中改善血小板与纤维蛋白原的结合和流动下的聚集。在不存在FXIII-A的情况下,血小板显示对激动剂刺激的敏感性降低,包括P-选择素暴露和纤维蛋白原结合降低。我们表明,FXIII-A参与血小板扩散,其中缺乏FXIII-A降低了血小板在纤维蛋白原和胶原蛋白上完全扩散的能力。我们的数据表明,血小板FXIII-A是重要的凝块收缩,在它的情况下形成的凝块收缩到较小的程度。总之,本研究表明,血小板FXIII-A在血栓形成过程中的功能,除了其抗纤维蛋白溶解作用外,还有助于血小板活化和血栓回缩。血小板因子XIII-A(FXIII-A)在血小板内大量存在。本研究检查和表征FXIII-A在血小板活化中的作用。血小板FXIII-A调节血小板活化和血小板对刺激的敏感性。血小板FXIII-A参与调节血凝块压实和凝块稳定性。
Factor XIII (FXIII) is an important proenzyme in the hemostatic system. The plasma-derived enzyme activated FXIII cross-links fibrin fibers within thrombi to increase their mechanical strength and cross-links fibrin to fibrinolytic inhibitors, specifically α2-antiplasmin, to increase resistance to fibrinolysis. We have previously shown that cellular FXIII (factor XIII-A [FXIII-A]), which is abundant in the platelet cytoplasm, is externalized onto the activated membrane and cross-links extracellular substrates. The contribution of cellular FXIII-A to platelet activation and platelet function has not been extensively studied. This study aims to identify the role of platelet FXIII-A in platelet function. We used normal healthy platelets with a cell permeable FXIII inhibitor and platelets from FXIII-deficient patients as a FXIII-free platelet model in a range of platelet function and clotting tests. Our data demonstrate that platelet FXIII-A enhances fibrinogen binding to the platelet surface upon agonist stimulation and improves the binding of platelets to fibrinogen and aggregation under flow in a whole-blood thrombus formation assay. In the absence of FXIII-A, platelets show reduced sensitivity to agonist stimulation, including decreased P-selectin exposure and fibrinogen binding. We show that FXIII-A is involved in platelet spreading where a lack of FXIII-A reduces the ability of platelets to fully spread on fibrinogen and collagen. Our data demonstrate that platelet FXIII-A is important for clot retraction where clots formed in its absence retracted to a lesser extent. Overall, this study shows that platelet FXIII-A functions during thrombus formation by aiding platelet activation and thrombus retraction in addition to its antifibrinolytic roles. Platelet factor XIII-A (FXIII-A) is present in abundance inside platelets. This study examines and characterises the roles of FXIII-A in platelet activation. Platelet FXIII-A regulates platelet activation and platelet sensitivity to stimulation. Platelet FXIII-A is involved in regulating blood clot compaction and clot stability.
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