Coagulation-associated enhancement of fibrinolytic activity via a neutralization of PAI-1 activity
Coagulation-associated enhancement of fibrinolytic activity via a neutralization of PAI-1 activity
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DOI：
10.1055/s-2000-9801
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发表时间：
2000-01-01
影响因子：
5.7
通讯作者：
Takada, A
中科院分区：
文献类型：
--
作者：
Urano, T;Ihara, H;Takada, A
组织纤溶酶原激活物和纤溶酶原激活物抑制物1(PAI-1)之间的平衡微调了血管中的总纤溶活性，虽然PAI-1以纤溶酶原激活物为靶标，但它也与其他丝氨酸蛋白酶如凝血酶和Xa因子反应，后者被证明只有在生理浓度的钙离子(Ca++)存在时才与PAI-1相互作用。通过这种相互作用，凝血酶和钙结合因子Xa通过中和PAI-1活性而缩短了纯化系统中纤维蛋白凝块的溶解时间，普通肝素和玻璃素都进一步促进了凝块的溶解。与我们实验室以前报道的人中性粒细胞弹性蛋白酶对PAI-1的切割和失活一起，这些丝氨酸蛋白酶对PAI-1活性的这种中和作用被证明与凝血相关的纤溶活性的增强密切相关。
Total fibrinolytic activity in the vasculature is finely tuned by the balance between tissue plasminogen activator and plasminogen activator inhibitor type 1 (PAI-1), Although PAI-1 targets plasminogen activators, it also reacts with other serine proteases such as thrombin and factor Xa, The latter was shown to interact with PAI-1 only when a physiological concentration of calcium ions (Ca++) is present. Through such interaction, thrombin and Ca++-bound factor Xa shortened fibrin clot lysis times in a purified system by neutralizing PAI-1 activity, Both unfractionated heparin and vitronectin were shown to enhance the clot lysis further. Together with the cleavage and inactivation of PAI-1 by human neutrophil elastase, which was reported previously from our laboratory, such neutralization of PAI-1 activity by these serine proteases was shown to be strongly involved in the coagulation-associated enhancement of fibrinolytic activity.