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Clearance of coagulation factor VIII in very low-density lipoprotein receptor knockout mice

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Author: Bovenschen, N. · Dijk, K.W. van · Havekes, L.M. · Mertens, K. · Vlijmen, B.J.M. van
Type:article
Date:2004
Institution: Gaubius Instituut TNO
Source:British Journal of Haematology, 5, 126, 722-725
Identifier: 237975
doi: doi:10.1111/j.1365-2141.2004.05093.x
Keywords: Biology · Biomedical Research · Clearance · Factor VIII · Knockout mice · Low-density lipoprotein receptor-related protein · Very low-density lipoprotein receptor · blood clotting factor 8 · cholesterol · triacylglycerol · very low density lipoprotein receptor · animal experiment · article · catabolism · cholesterol blood level · controlled study · knockout mouse · male · mouse · nonhuman · plasma clearance · priority journal · triacylglycerol blood level · Animals · Factor VIII · Integrases · LDL-Receptor Related Proteins · Mice · Mice, Knockout · Mice, Transgenic · Receptors, LDL

Abstract

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. Chemicals / CAS: blood clotting factor 8, 9001-27-8; cholesterol, 57-88-5; Cre recombinase, EC 2.7.7.-; Factor VIII, 9001-27-8; Integrases, EC 2.7.7.-; LDL-Receptor Related Proteins; Receptors, LDL; VLDL receptor