Effect of chemical modification induced by copper oxidation on lipoprotein (a) binding site function

High Lp(a)level in human serum appears to be associated with increased risk for athero- thrombosis. Pathogenecity of Lp(a) as a risk factor may depend on its lysine binding site [LBS] activity, which imparts a unique function to Lp(a), including a potential to inhibit fibrinolysis. Lp(a) is present in human plasma in four heterogeneous subspecies: (Lp(a)Lys-, Lp(a)Lys+1, Lp(a)Lys+2, Lp(a)Lys+3). This subclassification is made according to their ability to bind to lysine sepharose. Data available indicate that serum lipoproteins are sensitive to copper-induced oxidation. In this study the effect of copper oxidation on lysine binding site properties of Lp(a) was investigated, to find information about molecular mechanism of Lp(a) in promoting thrombosis and atherosclerosis. Serum lipids were oxidized in the presence of 15,30,50,75 and 100 µm of CuCl2. Lipid oxidation was measured as conjugated diene formation determined by spectrophotometric method at 245 nm. Four species of Lp(a) in the oxidized serum were isolated using affinity chromatography on lysine sepharose. Results showed a concentration-dependent increase in all subtypes of Lp(a)Lys+ and a decrease in all subtypes of Lp(a) Lys-. These data suggest that copper ion can induce a chemical modificaton to lipoprotein(a) leading to an increase in LBS activity of Lp(a), and thus, can promote athero- thrombosis.