Glycation of LDL in non-diabetic people: Small dense LDL is preferentially glycated both in vivo and in vitro

Abstract

Objective: LDL atherogenicity is frequently attributed to oxidative modification, but glycated LDL, which can participate in many of the cellular processes leading to atherosclerosis, generally circulates at higher concentration even in non-diabetic people. We tested the hypothesis that small-dense LDL, known to be most closely associated with coronary heart disease, undergoes more glycation than other LDL sub-fractions.

Methods and results: The concentration of glycated apolipoprotein B (apo B) was measured in serum, LDL and its sub-fractions from 44 non-diabetic subjects. By ELISA serum glycated apoB concentration was 3.0+/-1.1mg/dl (mean+/-S.D.) of which 84.6+/-13.6% was in LDL. Of the glycated apo B in LDL 67.8+/-21.9% was in small dense LDL (LDL3; D1.044-1.063g/ml) whereas only 32.2+/-21.9% was in more buoyant LDL subfractions (LDL1 and 2; D1.019-1.044g/ml). The percentage of apo B present in LDL1 and 2 which was glycated was 1.8+/-1.8% whereas in LDL3 it was 17.4+/-18.5% (P<0.001). Furthermore when LDL sub-fractions from non-diabetics (n=29) were incubated with glucose (30-80mmol/l) glycation of apo B in the denser LDL3 subfraction was significantly more pronounced than in less dense LDL subfractions.

Conclusion: Small-dense LDL is more susceptible to glycation and this may contribute to the atherogenicity of small-dense LDL, even in non-diabetic people.