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Low-density lipoprotein receptor-related protein catabolizes Factor VIII and Factor VIIIa using different modes of interaction.

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • JH Kurasawa
  • SA Shestopal
  • TK Lee
  • AG Sarafanov


It was shown previously that the low-density lipoprotein receptor-related protein (LRP), a member of the low-density lipoprotein receptor (LDLR) family, binds to coagulation factor VIII (FVIII) in vitro. In the present study, we tested if both FVIII and its activated form (FVIIIa) bind to LRP in a similar manner. The results showed that FVIIIa bound to an additional region in LRP, indicating that upon FVIII activation the binding capacity of LRP increases. To confirm these results, we tested the binding of a remnant of the activated form (FVIIIa heterodimer) and found that it also bound to the same additional region in LRP. Finally, we tested the half-life of FVIII and the FVIIIa heterodimer in mice. The results showed that the FVIIIa heterodimer is cleared approximately twice faster than FVIII. The clearance of the FVIIIa heterodimer was inhibited by the alpha-2-macroglobulin receptor-associated protein (RAP), which is a universal ligand of the LDLR family. This confirmed that the faster clearance of the FVIIIa heterodimer involves a receptor(s) from the LDLR family, likely LRP. In turn, this indicates that LRP catabolizes FVIII and FVIIIa using different modes of interaction, in accordance with our in vitro data.

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