Carboxypeptidase U (TAFIa) prevents lysis from proceeding into the propagation phase through a threshold‐dependent mechanism
Carboxypeptidase U (TAFIa) prevents lysis from proceeding into the propagation phase through a threshold‐dependent mechanism
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羧肽酶 U (TAFIa) 通过阈值依赖性机制防止裂解进入增殖阶段
DOI：
10.1111/j.1538-7836.2004.00605.x
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发表时间：
2004
影响因子：
10.4
通讯作者：
Dirk Hendriks
中科院分区：
文献类型：
--
作者：
J. Leurs;Viveca Nerme;Y. Sim;Dirk Hendriks
在体外人血浆凝块溶解模型中，凝血后凝血酶产生羧肽酶U（CPU），凝块溶解后期纤溶酶产生羧肽酶U（CPU）。CPU能够通过抑制组织型纤溶酶原激活剂（t-PA）激活纤溶酶原时部分降解纤维蛋白的辅因子活性来减缓凝块溶解。利用血栓调节蛋白和凝血酶抑制剂，在体外凝块溶解过程中CPU的产生可以在幅度和时间过程方面进行操纵。获得的数据表明，CPU通过阈值依赖性机制影响凝块溶解：只要CPU活性保持在阈值以上，就会阻止溶解进入增殖阶段。从CPU活性下降到低于该阈值的时刻起，裂解速率加速。CPU活动的阈值由t-PA浓度决定：增加t-PA浓度会增加CPU阈值，反之亦然。这意味着在纤维蛋白溶解能力较低时，CPU途径的作用将变得更加明显。我们基于阈值的假设表明，proCPU激活的时间过程、CPU的稳定性和t-PA浓度都在决定体外凝块溶解实验的结果中起着至关重要的作用。此外，这一假设为我们提供了对先前发表的关于CPU对高和低t-PA浓度的体外凝块溶解作用的数据的新见解。
Summary. In an in vitro clot lysis model in human plasma, carboxypeptidase U (CPU) is generated by thrombin following the coagulation and by plasmin at the later stage of clot lysis. CPU is able to slow down clot lysis by suppressing the cofactor activity of partially degraded fibrin in the plasminogen activation by tissue‐type plasminogen activator (t‐PA). Making use of thrombomodulin and a thrombin inhibitor, the generation of CPU during the in vitro clot lysis can be manipulated both in terms of magnitude and time course. The data obtained demonstrate that CPU affects the clot dissolution through a threshold‐dependent mechanism: as long as the CPU activity remains above the threshold value, lysis is prevented from proceeding into the propagation phase. From the moment the CPU activity drops below this threshold value, the rate of lysis accelerates. This threshold value for CPU activity is dictated by the t‐PA concentration: increasing the t‐PA concentration increases the CPU threshold and vice versa. This implies that the effect of the CPU pathway will become more apparent at a lower fibrinolytic capacity. Our threshold‐based hypothesis indicates that the time course of proCPU activation, the stability of CPU and the t‐PA concentration all play a crucial role in determining the result of the in vitro clot lysis experiment. Furthermore, this hypothesis provides us with new insights into previously published data on the effects of CPU on in vitro clot lysis by high and low t‐PA concentrations.