LIPOPROTEIN (A), COAGULATION AND FIBRINOLYSIS

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Lipoprotein (a) (Lp(a) is a form of low density lipoprotein. High levels of Lp(a) are highly correlated with atherosclerotic diseAse but the mechanism is unknown. It is the hypothesis of this application that, in part, this may be attributed to disorders in the fibrinolytic system induced by increased levels of Lp(a). Preliminary studies in this laboratory indicate that Lp(a) is a competitive inhibitor of plasminogen activation, that Lp(a) binds to one type of plasminogen activator, that Lp(a) blocks the binding of plasminogen to its receptor and that in normal subjects and patients with high Lp(a) levels the subunit molecular weight for apo(a) has a different distribution pattern. It is proposed to systematically study: 1) the effect of Lp(a) on plasminogen activation catalyzed by streptokinase-plasmin complexes, urokinase and tissue plasminogen activator; 2) the effect of Lp(a) levels on the binding of plasminogen to endothelial and monocyte-like (U-937) cells; 3) the effect of Lp(a) on the interaction of plasminogen with fibrin. As part of these studies, the direct binding of apo(a) with these cells will also be studied. The effect of Lp(a) on the binding of tissue plasminogen activator to endothelial cells and fibrin will also be examined.