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 alpha 2-macroglobulin (alpha 2M) 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 alpha 2M-proteinase complexes (alpha 2M*) also diminished the plasma clearance of 125I-factor Xa in a dose-dependent fashion. The clearance of preformed complexes of 125I-factor Xa and alpha 2M 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 alpha 2M.
Narita
M
M
Edward Mallinckrodt, Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA.
Rudolph
A E
AE
Miletich
J P
JP
Schwartz
A L
AL
D000818:Animals; D001777:Blood Coagulation; D015951:Factor Xa / Q000378:metabolism*; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D015951:Factor Xa