ENZYMATIC AND CHEMICAL MODIFICATIONS OF LIPOPROTEIN(A) SELECTIVELY ALTER ITS LYSINE-BINDING FUNCTIONS

The pathogenicity of lipoprotein(a) [Lp(a)] as a risk factor for cardi ovascular disease may depend upon its lysine binding sites (LBS) which impart unique functions to Lp(a) not shared with low density lipoprot ein. Biologically relevant modifications of Lp(a) were tested for alte rations of LBS activity using two previously described functional assa ys, a LBS-Lp(a) immunoassay and a lysine-Sepharose bead assay. In the LBS-Lp(a) immunoassay, minimal changes in the LBS activity of Lp(a) we re observed after modification with lipoprotein lipase, sphingomyelina se, or phospholipase C. In contrast, a significant(p < 0.003) increase in the LBS activity of Lp(a) occurred after phospholipase A(2) (PLA(2 )) treatment, and this increase was confirmed using the lysine-Sepharo se bead assay. The increase depended upon the release of fatty acids f rom Lp(a) by PLA(2). A decrease in the LBS activity of Lp(a) occurred after oxidation of Lp(a) with 2,2'-azobis(2-amidinopropane) dihydrochl oride (AAPH) (44% decrease), but CuSO4 oxidation increased LBS activit y (210%). N-acetyl-cysteine (NAC) treatment of Lp(a) decreased (48%) L BS activity while homocysteine treatment had no (89%) effect. Thus, mo dification of phospholipids and protein moieties can alter the I,BS-ac tivity of LF(a). Such enzymatic and chemical modifications may contrib ute to the variability in LBS function of Lp(a) seen within the popula tion. (C) 1998 Elsevier Science B.V. All rights reserved.