Lipoprotein(a), fibrin binding, and plasminogen activation.
Lipoprotein(a) (Lp[a]) is a complex plasma lipoprotein in which apolipoprotein (apo) B-100 is covalently linked by a disulfide bridge to a unique apolipoprotein, apo(a). The cDNA of apo(a) has recently been isolated and sequenced, and a remarkable homology to human plasminogen has been noted. In this report, we demonstrate that, like plasminogen, Lp(a) binds to fibrin. In addition, Lp(a) competes with plasminogen and tissue-type plasminogen activator for fibrin binding. As a functional consequence of these binding properties, we show that Lp(a) attenuates the fibrin-dependent enhancement of tissue-type plasminogen activator activity against the native substrate, and does so as an uncompetitive inhibitor (Ki = 15 nM). Finally, we show that in a plasma milieu, Lp(a) attenuates clot lysis induced by tissue-type plasminogen activator. None of these effects was noted with low density lipoprotein free of apo(a). These data suggest that Lp(a) influences the fibrinolytic system and probably does so by virtue of the fibrin binding properties conferred by the kringle repeats of apo(a).
Loscalzo
J
J
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Weinfeld
M
M
Fless
G M
GM
Scanu
A M
AM
D001667:Binding, Competitive; D001777:Blood Coagulation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D005337:Fibrin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000378:metabolism* / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000302:isolation & purification; D010958:Plasminogen / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D007457:Iodine Radioisotopes; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator