The Low-Density Lipoprotein Receptor-Related Protein (LRP) Mediates Clearance of Coagulation Factor Xa In Vivo

Blood coagulation factor X plays a pivotal role in the clotting cascade. When administered intravenously to mice, the majority of activated factor X (factor Xa) binds to α2-macroglobulin (α2M) and is rapidly cleared from the circulation into liver. We show here that the low-density lipoprotein receptor-related protein (LRP) is responsible for factor Xa catabolism in vivo. Mice overexpressing a 39-kD receptor-associated protein that binds to LRP and inhibits its ligand binding activity displayed dramatically prolonged plasma clearance of 125I-factor Xa. Preadministration of α2M-proteinase complexes (α2M*) also diminished the plasma clearance of125I-factor Xa in a dose-dependent fashion. The clearance of preformed complexes of 125I-factor Xa and α2M was similar to that of 125I-factor Xa alone and was also inhibited by mice overexpressing a 39-kD receptor-associated protein. These results thus suggest that, in vivo, factor Xa is metabolized via LRP after complex formation with α2M.