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.
Department of Plasma Proteins, Sanquin Research at CLB, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands.
Niels
N
Bovenschen
Ko Willems
KW
van Dijk
Louis M
LM
Havekes
Koen
K
Mertens
Bart J M
BJ
van Vlijmen
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