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 αΥ 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. Mica 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 of ¹²⁵I-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.