Platelet glycoprotein V spatio-temporally controls fibrin formation.
Platelet glycoprotein V spatio-temporally controls fibrin formation.
复制标题
血小板糖蛋白 V 时空控制纤维蛋白形成。
DOI：
10.1038/s44161-023-00254-6
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Nieswandt,
中科院分区：
文献类型：
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作者：
Beck,Sarah;Öftering,Patricia;Li,Renhao;Hemmen,Katherina;Nagy,Magdolna;Wang,Yingchun;Zarpellon,Alessandro;Schuhmann,MichaelK;Stoll,Guido;Ruggeri,ZaverioM;Heinze,KatrinG;Heemskerk,JohanWM;Ruf,Wolfram;Stegner,David;Nieswandt,
血管损伤部位的血小板活化和凝血对于止血至关重要，但可促进血管病理中的血栓形成和炎症。在这里，我们描绘了一个意想不到的时空控制机制的凝血酶活性，是血小板编排和局部限制过度纤维蛋白形成后，最初的止血血小板沉积。在血小板活化过程中，丰富的血小板糖蛋白（GP）V被凝血酶裂解。我们证明，与遗传和药理学的方法，凝血酶介导的脱落GPV并不主要调节血小板活化血栓形成，而是有一个独特的功能后，血小板沉积，并特别限制凝血酶依赖性产生的纤维蛋白，血管血栓炎症的关键介质。通过特异性阻断GPV脱落，止血血小板功能的遗传或药理学缺陷意外减弱，表明凝血酶依赖性纤维蛋白生成的时空控制也代表了改善止血的潜在治疗靶点。
The activation of platelets and coagulation at vascular injury sites is crucial for hemostasis but can promote thrombosis and inflammation in vascular pathologies. Here, we delineate an unexpected spatio-temporal control mechanism of thrombin activity that is platelet orchestrated and locally limits excessive fibrin formation after initial hemostatic platelet deposition. During platelet activation, the abundant platelet glycoprotein (GP)V is cleaved by thrombin. We demonstrate, with genetic and pharmacological approaches, that thrombin-mediated shedding of GPV does not primarily regulate platelet activation in thrombus formation but rather has a distinct function after platelet deposition and specifically limits thrombin-dependent generation of fibrin, a crucial mediator of vascular thrombo-inflammation. Genetic or pharmacologic defects in hemostatic platelet function are unexpectedly attenuated by specific blockade of GPV shedding, indicating that the spatio-temporal control of thrombin-dependent fibrin generation also represents a potential therapeutic target to improve hemostasis.