Abstract
To investigat the mechanism of acceleration of atherogenesis in diabetes mellitus, oxidative modification of glycated LDL (low-density lipoproteins) induced by vascular endothelial cells were examined with or without the addition of an glycation inhibitor, aminoguanidine. Negative charge of glycated LDL was significantly increased by endothelial cell-modification (200.5±11.9% of control, n=8, p<0.01) as compared with the endotheliummodified native LDL. Similar results were obtained on the change in fluorescence, but there was no significant difference on the change in lipid peroxide contents between native and glycated lipoproteins. Dose-dependent inhibition was demonstrated by the addition of aminoguanidine on these parameters of modified LDLs. Further studies were performed to examine the effects of these modified lipoproteins on the cholesteryl ester accumulation in rat peritoneal macrophages and the effects of aminoguanidine on the binding between LDL and/or collagen and malondialdehydes. These results suggest that glycated LDL may be more atherogeric than native LDL in view of oxidative modification induced by vascular endothelial cells, and that aminoguanidine may be able to inhibit such complicated modifications of LDLs.
