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


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.
White-Adams
Tara C
TC
Division of Biomedical Engineering, Oregon Health & Science University School of Medicine, 3303 SW Bond Ave, Portland, OR 97239, USA.
Berny
Michelle A
MA
Tucker
Erik I
EI
Gertz
Jacqueline M
JM
Gailani
David
D
Urbanus
Rolf T
RT
de Groot
Philip G
PG
Gruber
András
A
McCarty
Owen J T
OJ
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D005172:Factor XI / Q000378:metabolism*; D006801:Humans; D019679:Kininogen, High-Molecular-Weight / Q000494:pharmacology; D026502:LDL-Receptor Related Proteins; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D010973:Platelet Adhesiveness; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
D019679:Kininogen, High-Molecular-Weight; D026502:LDL-Receptor Related Proteins; D008024:Ligands; D018110:Receptors, Lipoprotein; C098773:low density lipoprotein receptor-related protein 8; D005172:Factor XI; D015032:Zinc; D002118:Calcium