Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7372
Authors: Kiouptsi, Klytaimnistra
Grill, Alexandra
Mann, Amrit
Döhrmann, Mareike
Lillich, Maren
Jäckel, Sven
Malinarich, Frano
Formes, Henning
Manukyan, Davit
Subramaniam, Saravanan
Khandagale, Avinash
Karwot, Cornelia
Thal, Serge
Bosmann, Markus
Scharrer, Inge
Jurk, Kerstin
Reinhardt, Christoph
Title: Mice deficient in the anti-haemophilic coagulation factor VIII show increased von Willebrand factor plasma levels
Online publication date: 12-Jul-2022
Language: english
Abstract: Von Willebrand factor (VWF) is the carrier protein of the anti-haemophilic Factor VIII (FVIII) in plasma. It has been reported that the infusion of FVIII concentrate in haemophilia A patients results in lowered VWF plasma levels. However, the impact of F8-deficiency on VWF plasma levels in F8-/y mice is unresolved. In order to avoid confounding variables, we back-crossed F8-deficient mice onto a pure C57BL/6J background and analysed VWF plasma concentrations relative to C57BL/6J WT (F8+/y) littermate controls. F8-/y mice showed strongly elevated VWF plasma concentrations and signs of hepatic inflammation, as indicated by increased TNF-α, CD45, and TLR4 transcripts and by elevated macrophage counts in the liver. Furthermore, immunohistochemistry showed that expression of VWF antigen was significantly enhanced in the hepatic endothelium of F8-/y mice, most likely resulting from increased macrophage recruitment. There were no signs of liver damage, as judged by glutamate-pyruvate-transaminase (GPT) and glutamate-oxalacetate-transaminase (GOT) in the plasma and no signs of systemic inflammation, as white blood cell subsets were unchanged. As expected, impaired haemostasis was reflected by joint bleeding, prolonged in vitro clotting time and decreased platelet-dependent thrombin generation. Our results point towards a novel role of FVIII, synthesized by the liver endothelium, in the control of hepatic low-grade inflammation and VWF plasma levels.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-7372
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC0
Information on rights of use: https://creativecommons.org/publicdomain/zero/1.0/
Journal: PLOS ONE
12
8
Pages or article number: e0183590
Publisher: PLOS
Publisher place: San Francisco, California, US
Issue date: 2017
ISSN: 1932-6203
Publisher URL: http://dx.doi.org/10.1371/journal.pone.0183590
Publisher DOI: 10.1371/journal.pone.0183590
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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