ABSTRACT
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 micro m 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