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Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein

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Author: Schalkwijk, C.G. · Vermeer, M.A. · Stehouwer, C.D.A. · Koppele, J. te · Princen, H.M.G. · Hinsbergh, V.W.M. van
Institution: Gaubius Instituut TNO
Source:Biochimica et Biophysica Acta - Lipids and Lipid Metabolism, 2-3, 1394, 187-198
Identifier: 234668
doi: DOI:10.1016/S0005-2760(98)00112-X
Keywords: Biology · Advanced glycation end product · Diabetes · Low density lipoprotein · Methylglyoxal · Arginine · Cholesterol ester · Cytochrome c · Iodine 125 · Low density lipoprotein · Low density lipoprotein receptor · Lysine · Methylglyoxal · Monocyte chemotactic protein 1 · Oxidized low density lipoprotein · Superoxide · Vasculotropin · Controlled study · Fluorescence · Human · Human cell · Isotope labeling · Lipid metabolism · Macrophage · Plasma clearance · Priority journal · Receptor affinity · Animals · Cell Line · Chemistry, Physical · Cytochrome c Group · Electrochemistry · Endothelium, Vascular · Fibroblasts · Humans · Lipid Peroxidation · Lipid Peroxides · Lipoproteins, LDL · Macrophages · Malondialdehyde · Mice · Oxidation-Reduction · Pyruvaldehyde · Receptors, LDL · Superoxides · Thiobarbituric Acid Reactive Substances · Murinae


In patients with diabetes, non-enzymatic glycation of low-density lipoprotein (LDL) has been suggested to be involved in the development of atherosclerosis. α-Dicarbonyl compounds were identified as intermediates in the non-enzymatic glycation and increased levels were reported in patients with diabetes. We studied the effect of the α-dicarbonyl compound methylglyoxal (MG) on the physicochemical and biological properties of LDL. MG dose-dependently modifies LDL, as indicated by the formation of fluorescent products and the increase of a net negative charge. MG (10 mmol/l) induced major modifications of arginine residues (up to 85%) and minor lysine modifications (less than 6%). MG-LDL preparations generated small amounts of superoxide anion radicals as measured by the reduction of cytochrome c, but this was not accompanied by peroxidation of the polyunsaturated fatty acids of MG-LDL. MG-LDL showed diminished recognition and uptake by the human LDL receptor in cultured cells and a markedly increased plasma clearance rate in vivo in rats. The reduced association and degradation of 125I-oxidised LDL by murine macrophages indicates recognition of MG-LDL by a scavenger receptor. Surprisingly, MG-LDL caused significantly less cholesteryl ester synthesis in murine macrophages, as compared to native LDL and oxidised or acetylated LDL. Highly modified MG-LDL did not induce activation of human endothelial cells, as measured by the expression of monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1. Copyright (C) 1998 Elsevier Science B.V.