Glucosylated glycerophosphoethanolamines are the major LDL glycation products and increase LDL susceptibility to oxidation - Evidence of their presence in atherosclerotic lesions

Glycation of both protein and lipid components is believed to be involved i n LDL oxidation. However, the relative importance of lipid and protein glyc ation in the oxidation process has not been established, and products of li pid glycation have not been isolated. Using glucosylated phosphatidylethano lamine (Glc PtdEtn) prepared synthetically, we have identified glycated dia cyl and alkenylacyl species among the ethanolamine phospholipids in LDL. Ac cumulation of these glycation products in LDL incubated with glucose showed a time- and glucose concentration-dependent increase. LDL specifically enr iched with Glc PtdEtn (25 nmol/mg protein) showed increased susceptibility to lipid oxidation when dialyzed against a 5-mu mol/L Cu2+ solution. The pr esence of this glucosylated lipid resulted in a 5-fold increase in producti on of phospholipid-bound hydroperoxides and 4-fold increase in phospholipid -bound aldehydes. Inclusion of glucosylated phosphatidylethanolamine in the surface lipid monolayer of the LDL resulted in rapid loss of polyunsaturat ed cholesteryl esters from the interior of the particle during oxidation. G lycated ethanolamine phospholipids were also isolated and identified from a therosclerotic plaques collected from both diabetic and nondiabetic subject s. The present findings provide direct evidence for the previously proposed causative effect of lipid glycation on LDL oxidation.