Identification of coagulation factor XI as a ligand for platelet apolipoprotein e receptor 2 (ApoER2)

Tara C. White-Adams, Michelle A. Berny, Erik I. Tucker, Jacqueline M. Gertz, David Gailani, Rolf T. Urbanus, Philip G. De Groot, András Gruber, Owen J.T. McCarty

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

OBJECTIVE-: Factor XI (FXI) promotes hemostasis and thrombosis through enhancement of thrombin generation and has been shown to play a critical role in the formation of occlusive thrombi in arterial injury models. The aim of this study was to investigate the mechanisms governing interactions between FXI and platelets. METHODS AND RESULTS-: Platelet adhesion to immobilized FXI was abrogated in the presence of the low-density lipoprotein (LDL) receptor antagonist, receptor-associated protein (RAP), soluble recombinant apolipoprotein E receptor 2 (ApoER2), or the LDL-binding domain 1 or 2 of ApoER2. FXI supported wild-type murine platelet binding; in contrast, ApoER2-deficient murine platelets did not adhere to FXI. In the presence of shear, platelet aggregates formed on FXI or activated FXI (FXIa) surfaces, whereas the presence of RAP, binding domain 1 of ApoER2, or an anti-GPIbα mAb blocked platelet adhesion to FXI or FXIa under shear. Soluble FXI bound to immobilized ApoER2′ with an affinity of 61 nmol/L. CONCLUSIONS-: This study has identified apolipoprotein E receptor 2 (ApoER2, LRP8), a member of the LDL receptor family, as a platelet receptor for FXI. The interaction of FXI with other cell types that express ApoER2 remains to be explored.

Original languageEnglish (US)
Pages (from-to)1602-1607
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number10
DOIs
StatePublished - Oct 1 2009

Keywords

  • Apolipoprotein E receptor 2
  • Factor XI
  • GPIb
  • LRP8
  • Platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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