In vivo regulation of plasminogen function by plasma carboxypeptidase B

Summary. 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.

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Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U)

Bouma

Meijers

2003

Journal of Thrombosis and Haemostasis

169

100

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TAFI and wound healing: closing a knowledge gap

Boffa

2003

Journal of Thrombosis and Haemostasis

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Impaired healing of cutaneous wounds and colonic anastomoses in mice lacking thrombin-activatable fibrinolysis inhibitor

Velde

Wagenaar²,

Reijerkerk³

et al. 2003

Journal of Thrombosis and Haemostasis

115

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Plasmin and other components of the plasminogen activation system play an important role in tissue repair by regulating extracellular matrix remodeling, including fibrin degradation. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase that, after activation, can attenuate plasmin-mediated fibrin degradation by removing the C-terminal lysine residues from fibrin, which play a role in the binding and activation of plasminogen. To test the hypothesis that TAFI is an important determinant in the control of tissue repair, we investigated the effect of TAFI deficiency on the healing of cutaneous wounds and colonic anastomoses. Histological examination revealed inappropriate organization of skin wound closure in the TAFI knockout mice, including an altered pattern of epithelial migration. The time required to completely heal the cutaneous wounds was slightly delayed in TAFI-deficient mice. Healing of colonic anastomoses was also impaired, as reflected by decreased strength of the tissue at the site of the suture, and by bleeding complications in 3 of 14 animals. Together, these abnormalities resulted in increased mortality in TAFI-deficient mice after colonic anastomoses. Although our study shows that tissue repair, including re-epithelialization and scar formation, occurs in TAFI-deficient mice, TAFI appears to be important for appropriate organization of the healing process.

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In vivo regulation of plasminogen function by plasma carboxypeptidase B

Cited by 15 publications

References 40 publications

Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U)

Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U)

TAFI and wound healing: closing a knowledge gap

Impaired healing of cutaneous wounds and colonic anastomoses in mice lacking thrombin-activatable fibrinolysis inhibitor

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