Clearance of coagulation factor VIII in very low-density lipoprotein receptor knockout mice.
Low-density lipoprotein receptor-related protein (LRP) contributes to factor VIII (FVIII) catabolism in vivo. Besides LRP, FVIII also interacts with very low-density lipoprotein receptor (VLDLR) in vitro. We investigated the physiological role of VLDLR in FVIII catabolism, using knockout mouse models for VLDLR and LRP, alone and in combination. VLDLR(-/-) mice displayed normal plasma FVIII, whereas VLDLR(-/-) LRP(-) double-knockout mice had slightly increased FVIII compared with LRP-deficient mice. Remarkably, VLDLR deficiency slightly accelerated FVIII clearance. Adenovirus-mediated overexpression of VLDLR did not lower plasma FVIII in LRP-deficient mice. We conclude that VLDLR does not act in concert with LRP in FVIII clearance in vivo.
Bovenschen
Niels
N
Department of Plasma Proteins, Sanquin Research at CLB, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands.
van Dijk
Ko Willems
KW
Havekes
Louis M
LM
Mertens
Koen
K
van Vlijmen
Bart J M
BJ
D000818:Animals; D005169:Factor VIII / Q000378:metabolism*; D019426:Integrases / Q000235:genetics; D026502:LDL-Receptor Related Proteins / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011973:Receptors, LDL / Q000097:blood / Q000235:genetics*
D026502:LDL-Receptor Related Proteins; D011973:Receptors, LDL; C036053:VLDL receptor; D005169:Factor VIII; C045073:Cre recombinase; D019426:Integrases