von Willebrand factor elevates plasma factor VIII without induction of factor VIII messenger RNA in the liver.
Factor VIII and von Willebrand factor (vWF) circulate in the plasma as a noncovalent protein complex. Circulating levels of factor VIII are coordinately regulated with circulating levels of vWF in which the ratio is maintained at 1 molecule of factor VIII for 50 to 100 vWF subunits. Infusion of vWF into vWF-deficient animal models and human patients yields a secondary increase in circulating levels of factor VIII. We have studied the mechanism of the secondary rise in factor VIII in a porcine model of vWF deficiency. On infusion of vWF into a vWF-deficient pig there was an approximately fivefold increase in circulating factor VIII activity. Liver biopsies were taken pre- and post-vWF infusion for isolation of total messenger RNA (mRNA). Factor VIII-specific mRNA was measured by an RNAse protection assay. The results showed no difference in the liver-specific factor VIII mRNA on vWF infusion. These results indicate that the secondary rise in factor VIII levels in response to exogenous vWF infusion is not dependent on increased steady-state levels of factor VIII mRNA in the liver.
Kaufman
R J
RJ
Howard Hughes Medical Institute and the Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. kaufmanr@umich.edu
Dorner
A J
AJ
Fass
D N
DN
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004195:Disease Models, Animal; D005169:Factor VIII / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis*; D012260:Ribonucleases; D013552:Swine; D014842:von Willebrand Diseases / Q000097:blood / Q000235:genetics / Q000628:therapy; D014841:von Willebrand Factor / Q000008:administration & dosage / Q000494:pharmacology*
D012333:RNA, Messenger; D014841:von Willebrand Factor; D005169:Factor VIII; D012260:Ribonucleases