Petri, A; Sasikumar, P; Folgado, PB; Jones, D; Xu, Y; Ahnström, J; Salles-Crawley, II; Crawley, JTB
(2024)
TFPIα anticoagulant function is highly dependent on protein S in vivo.
Sci Adv, 10 (5).
eadk5836.
ISSN 2375-2548
https://doi.org/10.1126/sciadv.adk5836
SGUL Authors: Salles-Crawley, Isabelle Irene
Abstract
Tissue factor pathway inhibitor α (TFPIα) is the major physiological regulator of the initiation of blood coagulation. In vitro, TFPIα anticoagulant function is enhanced by its cofactor, protein S. To define the role of protein S enhancement in TFPIα anticoagulant function in vivo, we blocked endogenous TFPI in mice using a monoclonal antibody (14D1). This caused a profound increase in fibrin deposition using the laser injury thrombosis model. To explore the role of plasma TFPIα in regulating thrombus formation, increasing concentrations of human TFPIα were coinjected with 14D1, which dose-dependently reduced fibrin deposition. Inhibition of protein S cofactor function using recombinant C4b-binding protein β chain significantly reduced the anticoagulant function of human TFPIα in controlling fibrin deposition. We report an in vivo model that is sensitive to the anticoagulant properties of the TFPIα-protein S pathway and show the importance of protein S as a cofactor in the anticoagulant function of TFPIα in vivo.
Item Type: |
Article
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Additional Information: |
Copyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
https://creativecommons.org/licenses/by/4.0/
This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: |
Humans, Animals, Mice, Anticoagulants, Blood Coagulation, Lipoproteins, Fibrin, Animals, Humans, Mice, Lipoproteins, Fibrin, Anticoagulants, Blood Coagulation |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Sci Adv |
ISSN: |
2375-2548 |
Language: |
eng |
Dates: |
Date | Event |
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2 February 2024 | Published | 4 January 2024 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
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PubMed ID: |
38306422 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/116223 |
Publisher's version: |
https://doi.org/10.1126/sciadv.adk5836 |
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