Insoluble complex formation of lipoprotein (a) with low density lipoprotein in the presence of calcium ions.

We investigated whether apolipoprotein B-containing lipoproteins could bind to the insoluble complexes of lipoprotein (a) (Lp(a)) induced by Ca2+. Lp(a), but not low density lipoprotein (LDL), very low density lipoprotein (VLDL), or high density lipoprotein3 (HDL3) formed insoluble complexes at physiologic Ca2+ concentrations. Desialylation of Lp(a) dramatically decreased the ability of Lp(a) to aggregate, suggesting that sialic acids on Lp(a) were responsible for forming Ca2+ cross-bridges. Since a reduction of only 30% of the sialic acids on Lp(a) inhibited Ca(2+)-induced complex formation, it appears that only a small percentage of sialic acids on Lp(a) is involved in Ca(2+)-induced cross-bridging of Lp(a) particles. To determine whether other lipoproteins would complex to Lp(a) in the insoluble complexes, we mixed Lp(a) with LDL, VLDL, or HDL3 in the presence of Ca2+. Although both LDL and VLDL bound to the Lp(a) in the insoluble complexes, HDL3 not only did not bind, but it also prevented Lp(a) from forming insoluble complexes. LDL bound to Lp(a) in the insoluble complexes in a concentration-dependent manner, eventually reaching saturation at a molar ratio of 5:4 (LDL to Lp(a)). The interaction between LDL and Lp(a) appeared to be ionic, since increases in the positive charge on LDL by desialylation increased this interaction, whereas decreases in positive charge on LDL reduced this interaction. At higher Ca2+ concentrations, the binding of acetyl LDL to Lp(a) in the insoluble complexes was greater than that of LDL. Since more Ca2+ was required for concentration-dependent saturation of acetyl LDL binding, it is likely that Ca2+ cross-bridging was responsible for this binding. Thus, LDL, especially its modified forms, could contribute to the formation of insoluble complex of Lp(a) with Ca2+ in atherosclerotic lesions and help explain its preferential accumulation there.