Alternatively spliced isoforms of tissue factor pathway inhibitor

Tissue factor pathway inhibitor (TFPI) is the major regulator of tissue factor (TF)-induced coagulation. It down regulates coagulation by binding to the TF/fVIIa complex in a fXa dependent manner. It is predominantly produced by microvascular endothelial cells, though it is also found in platelets,...

Full description

Bibliographic Details
Main Authors: Maroney, S., Ellery, Paul, Mast, A.
Format: Journal Article
Published: Pergamon 2010
Online Access:http://hdl.handle.net/20.500.11937/18159
_version_ 1848749665231568896
author Maroney, S.
Ellery, Paul
Mast, A.
author_facet Maroney, S.
Ellery, Paul
Mast, A.
author_sort Maroney, S.
building Curtin Institutional Repository
collection Online Access
description Tissue factor pathway inhibitor (TFPI) is the major regulator of tissue factor (TF)-induced coagulation. It down regulates coagulation by binding to the TF/fVIIa complex in a fXa dependent manner. It is predominantly produced by microvascular endothelial cells, though it is also found in platelets, monocytes, smooth muscle cells, and plasma. Its physiological importance is demonstrated by the embryonic lethality observed in TFPI knockout mice and by the increase in thrombotic burden that occurs when heterozygous TFPI mice are bred with mice carrying genetic risk factors for thrombotic disease, such as factor V Leiden. Multiple TFPI isoforms, termed TFPIa, TFPIß, and TFPId in humans and TFPIa, TFPIß, and TFPI? in mice, have been described, which differ in their domain structure and method for cell surface attachment. A significant functional difference between these isoforms has yet to be described in vivo. Both human and mouse tissues produce, on average, approximately 10 times more TFPIa message when compared to that of TFPIß. Consistent with this finding, several lines of evidence suggest that TFPIa is the predominant protein isoform in humans. In contrast, recent work from our laboratory demonstrates that TFPIß is the major protein isoform produced in adult mice, suggesting that TFPI isoform production is translationally regulated. © 2010 Elsevier Ltd. All rights reserved.
first_indexed 2025-11-14T07:24:33Z
format Journal Article
id curtin-20.500.11937-18159
institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T07:24:33Z
publishDate 2010
publisher Pergamon
recordtype eprints
repository_type Digital Repository
spelling curtin-20.500.11937-181592018-03-29T09:06:20Z Alternatively spliced isoforms of tissue factor pathway inhibitor Maroney, S. Ellery, Paul Mast, A. Tissue factor pathway inhibitor (TFPI) is the major regulator of tissue factor (TF)-induced coagulation. It down regulates coagulation by binding to the TF/fVIIa complex in a fXa dependent manner. It is predominantly produced by microvascular endothelial cells, though it is also found in platelets, monocytes, smooth muscle cells, and plasma. Its physiological importance is demonstrated by the embryonic lethality observed in TFPI knockout mice and by the increase in thrombotic burden that occurs when heterozygous TFPI mice are bred with mice carrying genetic risk factors for thrombotic disease, such as factor V Leiden. Multiple TFPI isoforms, termed TFPIa, TFPIß, and TFPId in humans and TFPIa, TFPIß, and TFPI? in mice, have been described, which differ in their domain structure and method for cell surface attachment. A significant functional difference between these isoforms has yet to be described in vivo. Both human and mouse tissues produce, on average, approximately 10 times more TFPIa message when compared to that of TFPIß. Consistent with this finding, several lines of evidence suggest that TFPIa is the predominant protein isoform in humans. In contrast, recent work from our laboratory demonstrates that TFPIß is the major protein isoform produced in adult mice, suggesting that TFPI isoform production is translationally regulated. © 2010 Elsevier Ltd. All rights reserved. 2010 Journal Article http://hdl.handle.net/20.500.11937/18159 10.1016/j.thromres.2010.01.038 Pergamon restricted
spellingShingle Maroney, S.
Ellery, Paul
Mast, A.
Alternatively spliced isoforms of tissue factor pathway inhibitor
title Alternatively spliced isoforms of tissue factor pathway inhibitor
title_full Alternatively spliced isoforms of tissue factor pathway inhibitor
title_fullStr Alternatively spliced isoforms of tissue factor pathway inhibitor
title_full_unstemmed Alternatively spliced isoforms of tissue factor pathway inhibitor
title_short Alternatively spliced isoforms of tissue factor pathway inhibitor
title_sort alternatively spliced isoforms of tissue factor pathway inhibitor
url http://hdl.handle.net/20.500.11937/18159