STEROL EFFLUX IS IMPAIRED FROM MACROPHAGE FOAM CELLS SELECTIVELY ENRICHED WITH 7-KETOCHOLESTEROL

The aim of the present study was to investigate whether impairment of cholesterol efflux previously found from mouse peritoneal macrophages loaded with oxidized low density lipoprotein (OxLDL) could be ascribed to the presence of oxysterols in these cells, 7-Ketocholesterol (7KC) , the major oxysterol present in OxLDL-loaded cells, was selectively i ncorporated into unoxidized LDL, which was subsequently acetylated to produce a high uptake form, Mouse macrophages incubated with 7KC-enric hed acetylated LDL (7kAcLDL) did not reveal cytotoxicity judged by cel l protein and trypan blue exclusion, A large proportion of cellular 7K C was esterified, indicating that it is a substrate for acyl CoA: chol esterol acyltransferase. Cholesterol efflux from mouse macrophages loa ded with 7kAcLDL, using apoA-I as a sterol acceptor, was impaired in c ells containing >50 nmol of 7KC/mg of cell protein compared with cells loaded with oxysterol-free acetylated LDL, Thus impairment of cholest erol efflux could be reproduced in cells loaded with 7kAcLDL containin g similar proportions of 7KC as OxLDL, 7KC itself was exported very po orly, even when the levels of 7KC in the cells were low. These results suggest that oxysterols present in foam cells in vitro can affect rev erse sterol transport and may be potentially important in foam cell fo rmation in vivo.