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Mice deficient in the anti-haemophilic coagulation factor VIII show increased von Willebrand factor plasma levels
- Source :
- PLoS ONE, PLoS ONE, Vol 12, Iss 8, p e0183590 (2017)
- Publication Year :
- 2017
- Publisher :
- PLOS, 2017.
-
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.
- Subjects :
- Heredity
Physiology
Genetic Linkage
610 Medizin
lcsh:Medicine
Cardiovascular Medicine
Pathology and Laboratory Medicine
Biochemistry
Vascular Medicine
Mice
Animal Cells
hemic and lymphatic diseases
610 Medical sciences
Medicine and Health Sciences
lcsh:Science
Immune Response
Thrombin
Animal Models
Hematology
Body Fluids
Blood
Experimental Organism Systems
Cardiovascular Diseases
X-Linked Traits
Sex Linkage
Blood Coagulation Tests
Anatomy
Cellular Types
Research Article
Platelets
congenital, hereditary, and neonatal diseases and abnormalities
Immunology
Mouse Models
Hemorrhage
Enzyme-Linked Immunosorbent Assay
Research and Analysis Methods
Hemophilia A
Real-Time Polymerase Chain Reaction
Blood Plasma
Model Organisms
Signs and Symptoms
Diagnostic Medicine
von Willebrand Factor
Genetics
Animals
Hemophilia
Blood Coagulation
Inflammation
Clinical Genetics
Blood Cells
Coagulation Disorders
lcsh:R
Biology and Life Sciences
Proteins
Cell Biology
Mice, Inbred C57BL
lcsh:Q
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, PLoS ONE, Vol 12, Iss 8, p e0183590 (2017)
- Accession number :
- edsair.doi.dedup.....47fed2fce0e3afbfc59197058635402a
- Full Text :
- https://doi.org/10.25358/openscience-7372