Clearance of coagulation factor VIII in very low-density lipoprotein receptor knockout mice
article
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
Topics
Biomedical ResearchClearanceFactor VIIIKnockout miceLow-density lipoprotein receptor-related proteinVery low-density lipoprotein receptorblood clotting factor 8cholesteroltriacylglycerolvery low density lipoprotein receptoranimal experimentarticlecatabolismcholesterol blood levelcontrolled studyknockout mousemalemousenonhumanplasma clearancepriority journaltriacylglycerol blood levelAnimalsFactor VIIIIntegrasesLDL-Receptor Related ProteinsMiceMice, KnockoutMice, TransgenicReceptors, LDL
TNO Identifier
237975
ISSN
00071048
Source
British Journal of Haematology, 126(5), pp. 722-725.
Pages
722-725
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