Diminished rate of mouse peritoneal macrophage cholesterol efflux is not related to the degree of HDL glycation in diabetes mellitus

The efflux of C-14-cholesterol from mouse peritoneal macrophages mediated by in vivo and in vitro glycation of intact HDL3 and by HDL3 apolipoproteins was investigated. Cholesterol-laden cells were incubated a long time with HDL3 from control subjects (C), poorly controlled diabetes mellitus patients (D) and with HDL C submitted to in vitro glycation (G), as well as with all their respectively isolated apolipoproteins. A diminished cholesterol efflux rate occurred in incubations with intact HDL3 D but not with intact HDL(3)G or with apoHDL(3)C, G or D. the specific binding of I-125-HDL(3)G to the cell receptor, obtained upon incubation int he absence and in the presence of excess unlabelled HDL3, was lower than the control. The role of apoE secretion by cholesterol-laden macrophages on cholesterol efflux was analyzed by incubating apoE knockout and control mice macrophages with HDL C or HDL G: a lower cholesterol efflux was observed from apoE knockout macrophages but glycation of HDL3 did not influence this process either. The diminished capacity to remove cholesterol by the HDL drawn from diabetic subjects must be attributed to other modifications of the lipoproteins, except fro non enzymatic glycation. Thus, events that impair the cell cholesterol removal in diabetes mellitus are multifaceted. (C) 2000 Elsevier Science B.V. All rights reserved.