Significance of acidic sugar chains of apolipoprotein B-100 in cellular metabolism of low-density lipoproteins.

We have elucidated the carbohydrate structures of the N-linked sugar chains of human and rabbit apolipoprotein B-100 (apo B-100), which is similar in composition to oligosaccharides (Arch Biochem Biophys 1989;273:197-205, Arteriosclerosis 1990; 10:386-93). We have also shown the negative correlation of the ratio of acidic sugar chains of apo B-100 to the serum cholesterol levels in Watanabe heritable hyperlipidemic rabbits (Atherosclerosis 1992;93:229-35). The acidity of sugar chains is determined by the existence of sialic acid residues at the terminal of oligosaccharides. In the present study we investigated N-linked sugar chains of apo B-100 from patients with coronary artery disease (CAD) who had moderate hypercholesterolemia (less than 400 mg/dL). There was no difference in the structure of their oligosaccharides and the ratio of acidic sugar chains of apo B-100 from CAD patients as compared with that from healthy individuals reported previously. To clarify the role of sialic acid residues in apo B-100 for lipoprotein metabolism, we studied cellular uptake of low-density lipoproteins (LDLs) treated with sialidase (desialylated LDL). Desialylated LDLs were taken up and degraded to a 2-fold greater degree than control LDL by human monocyte-derived macrophages and stimulated cholesterol esterification in these cells. These results indicate that sialic acid residues of apo B- 100 play an important role in cellular uptake and degradation of LDL.