CELLULAR CHOLESTEROL EFFLUX MEDIATED BY CYCLODEXTRINS

In this study, we compared cholesterol efflux mediated by either high density lipoproteins (HDL(3)) or beta-cyclodextrins, cyclic oligosacch arides that are able to dis solve lipids in their hydrophobic core. be ta-Cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin, and methyl-beta-cy clodextrin at 10 mM induced the release of 50-90% of L-cell [H-3]chole sterol after 8 h of incubation, with a major portion of this cholester ol being released in the first 1-2 h of incubation. The cholesterol ef flux kinetics are different if cells are incubated with HDL(3), which induces a relatively constant rate of release of cholesterol throughou t an 8-h incubation. Cholesterol efflux to cyclodextrins was much grea ter than phospholipid release. To test the hypothesis that maximal eff lux rate constants for a particular cell are independent of the type o f acceptor, we estimated the maximal rate constants for efflux (V-max) of cellular cholesterol from L-cells, Fu5AH cells, and GM3468A fibrob lasts. The rate constant for HDL(3)-mediated efflux varied among cell lines in the order Fu5AH > L-cells > fibroblasts. However, these diffe rences were not evident when cyclodextrins were used as cholesterol ac cepters. The estimated V-max values for cyclodextrin-mediated efflux w ere 3.5-70-fold greater than for HDL(3) for the three cell lines. The very high efficiency of cyclodextrins in stimulating cell cholesterol efflux suggests that these compounds can be used in two general ways f or studies of atherosclerosis: 1) as research tools to probe mechanism s of cholesterol transport and aspects of membrane structure or 2) as potential pharmacological agents that could modify in vivo cholesterol metabolism and influence the development of the atherosclerotic plaqu e.