LIPOPROTEIN (A) REGULATES PLASMIN GENERATION AND INHIBITION

The relationship between lipoprotein (a) (Lp(a)) and atherosclerosis h as been appreciated for a number of years. Only in recent years, howev er, has the structural relationship of Lp(a) to plasminogen resulted i n studies of the effect of this lipoprotein on fibrinolysis. Lp(a) inh ibits 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 i t blocks activation of plasminogen by t-PA. u-PA-mediated activation o f plasminogen is blocked on surfaces including heparin and chondroitin sulfate. Lp(a) also favors inhibition of plasmin by alpha(2)-antiplas min (alpha(2)-AP). The ability of Lp(a) to compete with plasmin for fi brin 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 inhibitio n of t-PA by plasminogen activator type 1 in the presence of fibrinoge n or heparin. Thus, Lp(a) modulates most of the reactions involved in plasmin generation and inhibition. Its overall effect will depend prim arily on the concentrations of Lp(a), PAI-1 and t-PA in vivo.