Autoren:	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
Titel:	Mice deficient in the anti-haemophilic coagulation factor VIII show increased von Willebrand factor plasma levels
Online-Publikationsdatum:	12-Jul-2022
Erscheinungsdatum:	2017
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7372
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC0
Informationen zu den Nutzungsrechten:	https://creativecommons.org/publicdomain/zero/1.0/
Zeitschrift:	PLOS ONE 12 8
Seitenzahl oder Artikelnummer:	e0183590
Verlag:	PLOS
Verlagsort:	San Francisco, California, US
Erscheinungsdatum:	2017
ISSN:	1932-6203
URL der Originalveröffentlichung:	http://dx.doi.org/10.1371/journal.pone.0183590
DOI der Originalveröffentlichung:	10.1371/journal.pone.0183590
Enthalten in den Sammlungen:	DFG-OA-Publizieren (2012 - 2017)