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

Niels Bovenschen; Ko Willems van Dijk; Louis M Havekes; Koen Mertens; Bart J M van Vlijmen

doi:10.1111/j.1365-2141.2004.05093.x

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

Niels Bovenschen, Ko Willems van Dijk, Louis M Havekes, Koen Mertens, Bart J M van Vlijmen

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	722-5
Number of pages	4
Journal	British Journal of Haematology
Volume	126
Issue number	5
DOIs	https://doi.org/10.1111/j.1365-2141.2004.05093.x
Publication status	Published - Sept 2004
Externally published	Yes

Keywords

Animals
Factor VIII
Integrases
LDL-Receptor Related Proteins
Mice
Mice, Knockout
Mice, Transgenic
Receptors, LDL

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10.1111/j.1365-2141.2004.05093.x

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title = "Clearance of coagulation factor VIII in very low-density lipoprotein receptor knockout mice",

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.",

keywords = "Animals, Factor VIII, Integrases, LDL-Receptor Related Proteins, Mice, Mice, Knockout, Mice, Transgenic, Receptors, LDL",

author = "Niels Bovenschen and {van Dijk}, {Ko Willems} and Havekes, {Louis M} and Koen Mertens and {van Vlijmen}, {Bart J M}",

year = "2004",

month = sep,

doi = "10.1111/j.1365-2141.2004.05093.x",

language = "English",

volume = "126",

pages = "722--5",

journal = "British Journal of Haematology",

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publisher = "Wiley-Blackwell",

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TY - JOUR

T1 - Clearance of coagulation factor VIII in very low-density lipoprotein receptor knockout mice

AU - Bovenschen, Niels

AU - van Dijk, Ko Willems

AU - Havekes, Louis M

AU - Mertens, Koen

AU - van Vlijmen, Bart J M

PY - 2004/9

Y1 - 2004/9

N2 - 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.

AB - 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.

KW - Animals

KW - Factor VIII

KW - Integrases

KW - LDL-Receptor Related Proteins

KW - Mice

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Receptors, LDL

U2 - 10.1111/j.1365-2141.2004.05093.x

DO - 10.1111/j.1365-2141.2004.05093.x

M3 - Article

C2 - 15327526

SN - 0007-1048

VL - 126

SP - 722

EP - 725

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 5

ER -

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

Abstract

Keywords

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