Lipoprotein(a) inhibits plasminogen activation in a template-dependent manner.
Lipoprotein(a) [Lp(a)] is a low density lipoprotein whose plasma levels strongly correlate with the occurrence of atherosclerotic disease. Structural studies have demonstrated that Lp(a) contains two disulphide bonded subunits, one of which has structural similarity to plasminogen. This subunit, designed apo-lipoprotein(a), contains multiple repeat copies of a kringle homologous to kringle-4 of plasminogen, one copy of a kringle-5-like structure and a domain homologous to the catalytic light chain of plasmin. This subunit, however, lacks the site where plasminogen activators cleave plasminogen to generate the active proteinase. Recent studies demonstrate that Lp(a) competes with plasminogen for binding to endothelial cells and macrophages and thus prevents assembly of the fibrinolytic system on cell surfaces. Lp(a) also inhibits activation of plasminogen by streptokinase, urokinase-type plasminogen activator or tissue-type plasminogen activator (t-PA). Inhibition of plasminogen activation by t-PA requires the presence of a template on which activation occurs. This template can be either fibrin or heparin. This review considers the role of Lp(a) as an inhibitor of template-dependent activation of the fibrinolytic system.
Edelberg
J M
JM
Pizzo
S V
SV
D000818:Animals; D001777:Blood Coagulation; D005342:Fibrinolysis; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000494:pharmacology*; D010958:Plasminogen / Q000037:antagonists & inhibitors*; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors*
D017270:Lipoprotein(a); D008074:Lipoproteins; D010958:Plasminogen; D010959:Tissue Plasminogen Activator