Glycation of high-density lipoprotein does not increase its susceptibilityto oxidation or diminish its cholesterol efflux capacity

In vitro oxidation of high-density lipoprotein (HDL) diminishes its capacit y to mediate cholesterol efflux from J774 macrophages, To investigate the p ossible role of HDL glycation in the increased atherosclerotic risk in diab etes, we studied the effects of in vitro glycation of HDL on its susceptibi lity to oxidation and capacity to mediate cholesterol efflux, HDL isolated from normal volunteers was incubated with 25 mmol/L glucose for 70 hours, r esulting in 6.1% additional derivatization of apoproteins as determined by trinitrobenzene sulfonic acid (TNBS) reactivity. Unmodified HDL and glycate d HDL (glyHDL) were tested for susceptibility to oxidation by incubation wi th various concentrations of copper and three assays of lipid oxidation, Gl yHDL produced 51% to 64% less lipid peroxide than HDL as determined by reac tion with xylenol orange (P < .02), indicating decreased susceptibility to oxidation. However, glycation of HDL did not result in significant changes in the formation of conjugated dienes or thiobarbituric acid-reactive subst ances (TBARS), two other indices of oxidation, To study cholesterol efflux, J774 macrophages were labeled with H-3-cholesterol followed by incubation with the various HDL preparations. HDL and glyHDL had a similar capacity to mediate efflux. The efflux mediated by oxidized HDL (oxHDL) and oxidized g lyHDL was reduced to a similar extent compared with the efflux mediated by HDL and glyHDL. These data indicate that in vitro glycation of HDL does not increase its susceptibility to oxidation and does not diminish its capacit y to mediate cholesterol efflux. Copyright (C) 1999 by W.B. Saunders Compan y.