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Tissue factor pathway inhibitor: Structure, biology and involvement in disease

Tissue factor pathway inhibitor: Structure, biology and involvement in disease
Tissue factor pathway inhibitor: Structure, biology and involvement in disease
Tissue factor (TF)-initiated coagulation plays a significant role in the pathophysiology of many diseases, including cancer and inflammation. Tissue factor pathway inhibitor (TFPI) is a plasma Kunitz-type serine protease inhibitor, which modulates initiations of coagulation induced by TF. In a factor (F) Xa-dependent feedback system, TFPI binds directly and inhibits the TF-FVII/FVIIa complex. Normally, TFPI exists in plasma both as a full-length molecule and as variably carboxy-terminal truncated forms. TFPI also circulates in complex with plasma lipoproteins. The levels and the dual inhibitor effect of TFPI on FXa and TF-FVII/FVIIa complex offers insight into the mechanisms of various pathological conditions triggered by TF. The use of selective pharmacological inhibitors has become an indispensable tool in experimental haemostasis and thrombosis research. In vivo administration of recombinant TFPI (rTFPI) in an experimental animal model prevents thrombosis (and re-thrombosis after thrombolysis), reduces mortality from E. coli-induced-septic shock, prevents fibrin deposition on subendothelial human matrix and protects against disseminated intravascular coagulation (DIC). Thus, TFPI may play an important role in modulating TF-induced thrombogenesis and it may also provide a unique therapeutic approach for prophylaxis and/or treatment of various diseases. In this review, we consider structural and biochemical aspects of the TFPI molecule and detail its inhibitory mechanisms and therapeutic implications in various disease conditions.
tissue factor pathway inhibitor (TFPI), structure, biochemistry, thrombophilia, antithrombotic agent, review
1096-9896
327-339
Lwaleed, B.A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Bass, P.S.
8498593e-3539-4908-80da-e2606153869a
Lwaleed, B.A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Bass, P.S.
8498593e-3539-4908-80da-e2606153869a

Lwaleed, B.A. and Bass, P.S. (2006) Tissue factor pathway inhibitor: Structure, biology and involvement in disease. The Journal of Pathology, 208 (3), 327-339. (doi:10.1002/path.1871).

Record type: Article

Abstract

Tissue factor (TF)-initiated coagulation plays a significant role in the pathophysiology of many diseases, including cancer and inflammation. Tissue factor pathway inhibitor (TFPI) is a plasma Kunitz-type serine protease inhibitor, which modulates initiations of coagulation induced by TF. In a factor (F) Xa-dependent feedback system, TFPI binds directly and inhibits the TF-FVII/FVIIa complex. Normally, TFPI exists in plasma both as a full-length molecule and as variably carboxy-terminal truncated forms. TFPI also circulates in complex with plasma lipoproteins. The levels and the dual inhibitor effect of TFPI on FXa and TF-FVII/FVIIa complex offers insight into the mechanisms of various pathological conditions triggered by TF. The use of selective pharmacological inhibitors has become an indispensable tool in experimental haemostasis and thrombosis research. In vivo administration of recombinant TFPI (rTFPI) in an experimental animal model prevents thrombosis (and re-thrombosis after thrombolysis), reduces mortality from E. coli-induced-septic shock, prevents fibrin deposition on subendothelial human matrix and protects against disseminated intravascular coagulation (DIC). Thus, TFPI may play an important role in modulating TF-induced thrombogenesis and it may also provide a unique therapeutic approach for prophylaxis and/or treatment of various diseases. In this review, we consider structural and biochemical aspects of the TFPI molecule and detail its inhibitory mechanisms and therapeutic implications in various disease conditions.

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More information

Published date: 2006
Keywords: tissue factor pathway inhibitor (TFPI), structure, biochemistry, thrombophilia, antithrombotic agent, review

Identifiers

Local EPrints ID: 19319
URI: http://eprints.soton.ac.uk/id/eprint/19319
ISSN: 1096-9896
PURE UUID: 7e0bcecb-b654-4c09-9bcb-3b2bcfb55236
ORCID for B.A. Lwaleed: ORCID iD orcid.org/0000-0001-5748-4892

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Date deposited: 01 Feb 2006
Last modified: 06 Aug 2024 01:39

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Contributors

Author: B.A. Lwaleed ORCID iD
Author: P.S. Bass

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