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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:467.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Glucosylated Glycerophosphoethanolamines are the Major LDL Glycation Products and Increase LDL Susceptibility to Oxidation

Evidence of Their Presence in Atherosclerotic Lesions

Amir Ravandi; Arnis Kuksis; Nisar A. Shaikh

From the Department of Laboratory Medicine and Pathobiology (A.R., N.A.S.), and Banting and Best Department of Medical Research (A.R., A.K.), University of Toronto; and Spectral Diagnostics Inc (N.A.S.), Toronto, Canada.

Correspondence to Dr Arnis Kuksis, Banting and Best Department of Medical Research, University of Toronto, 112 College St, Toronto, Ontario M5G 1L6, Canada. E-mail arnis.kuksis{at}utoronto.ca

Abstract—Glycation of both protein and lipid components is believed to be involved in LDL oxidation. However, the relative importance of lipid and protein glycation in the oxidation process has not been established, and products of lipid glycation have not been isolated. Using glucosylated phosphatidylethanolamine (Glc PtdEtn) prepared synthetically, we have identified glycated diacyl and alkenylacyl species among the ethanolamine phospholipids in LDL. Accumulation of these glycation products in LDL incubated with glucose showed a time- and glucose concentration–dependent increase. LDL specifically enriched with Glc PtdEtn (25 nmol/mg protein) showed increased susceptibility to lipid oxidation when dialyzed against a 5-µmol/L Cu²⁺ solution. The presence of this glucosylated lipid resulted in a 5-fold increase in production 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 polyunsaturated cholesteryl esters from the interior of the particle during oxidation. Glycated ethanolamine phospholipids were also isolated and identified from atherosclerotic plaques collected from both diabetic and nondiabetic subjects. The present findings provide direct evidence for the previously proposed causative effect of lipid glycation on LDL oxidation.

Key Words: low-density lipoproteins • peroxidation, lipid • glycation, phospholipid • diabetes • atheroma

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