MODIFICATION OF LIPOPROTEIN(A) BY OXIDATION OR DESIALYLATION INFLUENCES ITS ABILITY TO COMPETE WITH PLASMINOGEN FOR BINDING TO THE EXTRACELLULAR-MATRIX

Lipoprotein(a) [Lp(a)], and to a lesser extent low-density lipoprotein (LDL), have been shown to compete with plasminogen for binding to the extracellular matrix (ECM). Evidence exists that modification of lipo proteins alters their atherogenic properties, Therefore in the present study the effect of modifying Lp(a) and LDL by copper-induced in vitr o oxidation on their ability to compete with plasminogen for binding t o the ECM was studied. Oxidation of Lp(a) resulted in increased compet itiveness for plasminogen binding. This effect was dependent on the Lp (a) concentration used, as well as the extent of oxidation. In the hig hest Lp(a) concentration used (100 nmol/l apo B100), inhibition of pla sminogen binding was further increased with almost 30% compared with n ative Lp(a). In contrast, oxidation of LDL resulted in an additional i nhibition of plasminogen binding of about 10% at all concentrations us ed. In separate experiments Lp(a) and LDL were modified by neuraminida se treatment. After desialylation a strong tendency for better competi tiveness of Lp(a) was observed. Desialylation of LDL had no effect on its ability to compete with plasminogen for binding to the ECM. Modifi cation of the additional and distinguishing apolipoprotein [i.e. apo(a )] in Lp(a) by oxidation and desialylation most likely explains the di fference in behaviour of Lp(a) and LDL. It is concluded that modificat ion by oxidation, and to a lesser extent desialylation, increases the anti-fibrinolytic potential of Lp(a).