Glycation of plasma low density lipoproteins increases interaction with arterial proteoglycans

The increased susceptibility to atherosclerosis of diabetic individuals, ma y result from diabetes-associated modification in plasma low density lipopr oteins (LDL) which enhance their interaction with arterial extracellular ma trix proteoglycans. Using a nonhuman primate model for human diabetes, stud ies were conducted to examine diabetes-induced changes in LDL. Plasma LDL w ere isolated from control (n = 4) and streptozotocin-induced diabetic (n = 3) cynomolgus macaques by differential ultracentrifugation. An in vitro bin ding assay was used to measure LDL interaction with arterial proteoglycans. Significantly more diabetic LDL bound to proteoglycans than control LDL (1 2.9 +/- 0.7 mu g LDL cholesterol/mu g proteoglycan versus 8.9 +/- 0.5 mu g LDL cholesterol/mu g proteoglycan (mean +/- S.E.M.), P < 0.005), Glycation of LDL, determined by fructosamine content, was significantly enhanced in d iabetic versus control animals (37 +/- 3.1 versus 20 +/- 1.5 mu mol/l (mean +/- S.E.M.) P < 0.005). The correlation coefficient between fructosamine c ontent of LDL and its binding to arterial proteoglycans was 0.95. No LDL co mpositional variables other than glycation correlated with proteoglycan bin ding. Removal of the glycated portion of LDL from diabetic animals returned LDL proteoglycan binding to normal. These data demonstrate that the diabet es induced glycation of LDL increases its proteoglycan binding properties: thus, a critical mechanism in atherosclerosis, enhanced LDL interaction wit h arterial proteoglycans, may be accelerated by the diabetic state. (C) 199 9 Elsevier Science Ireland Ltd. All rights reserved.