Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U)
Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U)
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DOI：
10.1046/j.1538-7836.2003.00329.x
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发表时间：
2003-07-01
影响因子：
10.4
通讯作者：
Meijers, JCM
中科院分区：
文献类型：
--
作者：
Bouma, BN;Meijers, JCM
最近，一种新的纤溶抑制物被报道，它在被凝血酶激活后抑制纤溶，因此被命名为TAFI(凝血酶激活的纤溶抑制物；EC 3.4.17.20)。激活的TAFI(TAFI)通过去除纤维蛋白中的羧基末端赖氨酸来抑制纤溶。这些羧基末端的赖氨酸在纤溶酶对纤维蛋白进行有限的蛋白分解时暴露，并作为纤溶酶原和组织型纤溶酶原激活剂(t-PA)赖氨酸结合部位的配体。这些赖氨酸被Tafia消除后，t-PA介导的纤溶酶原激活的纤维蛋白辅因子功能被取消，导致纤溶酶的生成速度降低，从而下调纤溶。本文对TAFI的特点进行了综述，重点介绍了TAFI的激活途径和TAFIa在纤溶抑制中的作用。然而，不能排除Tafi在生物学上还有其他尚未确定的功能。
Recently, a new inhibitor of fibrinolysis was described, which downregulated fibrinolysis after it was activated by thrombin, and was therefore named TAFI (thrombin-activatable fibrinolysis inhibitor; EC 3.4.17.20). TAFI turned out to be identical to the previously described proteins, procarboxypeptidase U, procarboxypeptidase R, and plasma procarboxypeptidase B. Activated TAFI (TAFIa) downregulates fibrinolysis by the removal of carboxy-terminal lysines from fibrin. These carboxy-terminal lysines are exposed upon limited proteolysis of fibrin by plasmin and act as ligands for the lysine-binding sites of plasminogen and tissue-type plasminogen activator (t-PA). Elimination of these lysines by TAFIa abrogates the fibrin cofactor function of t-PA-mediated plasminogen activation, resulting in a decreased rate of plasmin generation and thus downregulation of fibrinolysis. In this review, the characteristics of TAFI are summarized, with an emphasis on the pathways leading to activation of TAFI and the role of TAFIa in the inhibition of fibrinolysis. However, it cannot be ruled out that TAFI has other, as yet undefined, functions in biology.