Sialic acid-containing components of lipoproteins influence lipoprotein-proteoglycan interactions

Sialic acid is a negatively charged sugar associated with the protein and l ipid portions of lipoproteins. Sialic acid has been hypothesised to play an anti-atherogenic role in lipoprotein metabolism through the electrostatic inhibition of lipoprotein interactions with chondroitin-6-sulphate-rich art erial proteoglycans (APG). We conducted a series of studies using native an d modified lipoproteins (VLDL1 Sf 60-400, VLDL2 Sf 20-60, IDL1 Sf 16-20, ID L2 Sf 12-16, LDLA Sf 8-12, and LDLB Sf 0-8) that vary in their sialic acid content to examine the relationship between lipoprotein sialic acid content and its interaction with APG. Lipoprotein sialic acid was greatest in VLDL 1 and decreased progressively with particle density until the IDL2 fraction (VLDL1 > VLDL2 > IDL1 > IDL2 = LDLA = LDLB). The pattern of reactivity of each fraction with APG was different from the pattern observed for lipoprot ein sialic acid content (IDL2 > LDLA > LDLB > IDL1 > VLDL2 > VLDL1). Levels of sialic acid were lower in subjects with CHD as compared to control subj ects but the presence of CHD had no effect on lipoprotein-APG complex forma tion when sex and plasma triglyceride levels were taken into account. There was also no significant relationship between the lipoprotein sialic acid c ontent and the reactivity with APG within each lipoprotein fraction. Treatm ent of hypertriglyceridaemic subjects with ciprofibrate decreased lipoprote in-APG complex formation in all lipoprotein fractions. This was associated with a decrease in the total sialic acid content of apo B100-containing lip oproteins suggesting that the total sialic acid content of apo B100-contain ing lipoproteins has no influence on lipoprotein-APG complex formation. We next conducted in vitro experiments to manipulate LDL sialic acid content. Enzymatic removal of sialic acid from LDL with neuraminidase resulted in an increase in LDL-APG complex formation. This was accompanied by an increase in the exposure of free amino groups on LDL possibly due to disruption of interactions between free amino groups and sialic acid-containing component s on LDL. Increasing LDL sialic acid content through incubation with gangli oside resulted in a decrease in lipoprotein-APG complex formation without a ny changes in the exposure of free amino groups on I-DL. We conclude that t otal sialic acid content of lipoproteins is not a major determinant of thei r binding to APG. However, specific sialic acid-containing components on li poproteins can affect their interaction with APG. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.