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

White-Adams TC, Berny MA, Tucker EI, Gertz JM, Gailani D, Urbanus RT, de Groot PG, Gruber A, McCarty OJ
Arterioscler Thromb Vasc Biol. 2009 29 (10): 1602-7

PMID: 19661487 · PMCID: PMC2756776 · DOI:10.1161/ATVBAHA.109.187393

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-GPIb alpha 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.

MeSH Terms (13)

Animals Blood Platelets Calcium Factor XI Humans Kininogen, High-Molecular-Weight LDL-Receptor Related Proteins Ligands Mice Mice, Inbred C57BL Platelet Adhesiveness Receptors, Lipoprotein Zinc

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