Factor VIII expression in liver disease
- 1 January 2004
- journal article
- Published by Georg Thieme Verlag KG in Thrombosis and Haemostasis
- Vol. 91 (02), 267-275
- https://doi.org/10.1160/th03-05-0310
Abstract
Liver disease is associated with markedly elevated plasma factor VIII (FVIII) levels, whereas the synthesis of many other coagulation factors and proteins is reduced. In order to define the mechanism of FVIII increase, we have determined the expression levels of FVIII, both at mRNA and protein level, in patients with liver disease who underwent partial liver resection. In addition, the expression of von Willebrand factor (VWF) and low density lipoprotein receptor-related protein (LRP), proteins known for their ability to modulate FVIII plasma levels, were examined. Tissue samples for RNA extraction were obtained from 4 patients with cirrhosis, 9 patients with liver failure without cirrhosis and 6 patients with liver metastasis of a colon or rectum carcinoma (control group). In patients with liver cirrhosis hepatic FVIII and LRP mRNA levels were significantly lower than controls (p ≤ 0.010), while VWF mRNA was significantly higher (p ≤ 0.050). Immunohistochemical analysis revealed that cellular VWF protein distribution was also increased in cirrhotic livers compared to liver tissue from patients with non-cirrhotic liver disease. In cirrhotic tissue enlarged portal veins appeared to overgrow FVIII producing sinusoidal endothelial cells. Similarly, the number of LRP-producing cells appeared to be lower in cirrhotic tissue than in controls. The plasma concentration of both FVIII and VWF was significantly higher in patients with cirrhosis than control subjects (p = 0.038 and 0.010 respectively). These results demonstrate that elevated plasma FVIII levels in liver cirrhosis are associated with increased hepatic biosynthesis of VWF and decreased expression of LRP, rather than increased FVIII synthesis.Funding Information
- Dutch Thrombosis Research Foundation (# 20003)
This publication has 15 references indexed in Scilit:
- Elevated plasma factor VIII in a mouse model of low-density lipoprotein receptor–related protein deficiencyBlood, 2003
- Factor VIII – novel insights into form and functionBritish Journal of Haematology, 2002
- A Mathematical Model of Coagulation Factor VIII KineticsPathophysiology of Haemostasis and Thrombosis, 1996
- Distribution of the ?2-macroglobulin receptor/low density lipoprotein receptor-related protein in human tissuesCell and tissue research, 1992
- Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extractionAnalytical Biochemistry, 1987
- Distribution of factor VIII mRNA and antigen in human liver and other tissuesNature, 1985
- Human von Willebrand Factor (vWF): Isolation of Complementary DNA (cDNA) Clones and Chromosomal LocalizationScience, 1985
- Molecular cloning of a cDNA encoding human antihaemophilic factorNature, 1984
- Alterations of Factor VIII von Willebrand Factor in Clinical Conditions Associated with an Increase in its Plasma ConcentrationBritish Journal of Haematology, 1981
- Transection of the oesophagus for bleeding oesophageal varicesBritish Journal of Surgery, 1973