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Blood, 1 August 2005, Vol. 106, No. 3, pp. 906-912. Prepublished online as a Blood First Edition Paper on April 19, 2005; DOI 10.1182/blood-2004-11-4230. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-11-4230v1 106/3/906    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bovenschen, N. Articles by van Vlijmen, B. J. M. Search for Related Content PubMed PubMed Citation Articles by Bovenschen, N. Articles by van Vlijmen, B. J. M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY LDL receptor cooperates with LDL receptor–related protein in regulating plasma levels of coagulation factor VIII in vivo Niels Bovenschen, Koen Mertens, Lihui Hu, Louis M. Havekes, and Bart J. M. van Vlijmen From the Department of Plasma Proteins, Sanquin Research at CLB, Amsterdam, The Netherlands; TNO Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands; Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Departments of Internal Medicine, Cardiology, and Hematology, Leiden University Medical Center, Leiden, The Netherlands. Low-density lipoprotein (LDL) receptor (LDLR) and LDLR-related protein (LRP) are members of the LDLR family of endocytic receptors. LRP recognizes a wide spectrum of structurally and functionally unrelated ligands, including coagulation factor VIII (FVIII). In contrast, the ligand specificity of LDLR is restricted to apolipoproteins E and B-100. Ligand binding to the LDLR family is inhibited by receptor-associated protein (RAP). We have previously reported that, apart from LRP, other RAP-sensitive mechanisms contribute to the regulation of FVIII in vivo. In the present study, we showed that the extracellular ligand-binding domain of LDLR interacts with FVIII in vitro and that binding was inhibited by RAP. The physiologic relevance of the FVIII–LDLR interaction was addressed using mouse models of LDLR or hepatic LRP deficiency. In the absence of hepatic LRP, LDLR played a dominant role in the regulation and clearance of FVIII in vivo. Furthermore, FVIII clearance was accelerated after adenovirus-mediated gene transfer of LDLR. The role of LDLR in FVIII catabolism was not secondary to increased plasma lipoproteins or to changes in lipoprotein profiles. We propose that LDLR acts in concert with LRP in regulating plasma levels of FVIII in vivo. This represents a previously unrecognized link between LDLR and hemostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Finally, the LDL receptor joins in Steven L. Gonias Blood 2005 106: 770. [Full Text] [PDF] This article has been cited by other articles: S. Dasgupta, Y. Repesse, J. Bayry, A.-M. Navarrete, B. Wootla, S. Delignat, T. Irinopoulou, C. Kamate, J.-M. Saint-Remy, M. Jacquemin, et al. VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors Blood, January 15, 2007; 109(2): 610 - 612. [Abstract] [Full Text] [PDF]

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