title: Lipoprotein (a) regulates plasmin generation and inhibition.
abstract: The relationship between lipoprotein (a) (Lp(a)) and atherosclerosis has been appreciated for a number of years. Only in recent years, however, has the structural relationship of Lp(a) to plasminogen resulted in studies of the effect of this lipoprotein on fibrinolysis. Lp(a) inhibits activation of plasminogen by tissue-type (t-PA) and urinary-type (u-PA) plasminogen activators. These inhibitory reactions are surface-dependent. When Lp(a) binds to fibrin, fibrinogen, heparin or cells it blocks activation of plasminogen by t-PA. u-PA-mediated activation of plasminogen is blocked on surfaces including heparin and chondroitin sulfate. Lp(a) also favors inhibition of plasmin by alpha 2-antiplasmin (alpha 2-AP). The ability of Lp(a) to compete with plasmin for fibrin binding displaces plasmin into solution where alpha 2-AP rapidly inhibits this proteinase. These effects are all antifibrinolytic. Lp(a) also exhibits one profibrinolytic effect, since it blocks inhibition of t-PA by plasminogen activator type 1 in the presence of fibrinogen or heparin. Thus, Lp(a) modulates most of the reactions involved in plasmin generation and inhibition. Its overall effect will depend primarily on the concentrations of Lp(a), PAI-1 and t-PA in vivo.
authors.affiliation: Duke University Medical Center, Durham, NC 27710.
authors.forename: J
authors.initials: J
authors.lastname: Edelberg
authors.forename: S V
authors.initials: SV
authors.lastname: Pizzo
mesh_terms: D001161:Arteriosclerosis / Q000209:etiology; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism* / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D017270:Lipoprotein(a); D000979:alpha-2-Antiplasmin; D005337:Fibrin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator