DELAYED LOSS OF CHOLESTEROL FROM A LOCALIZED LIPOPROTEIN DEPOT IN APOLIPOPROTEIN A-I-DEFICIENT MICE

The anti-atherogenic role of high density lipoprotein is well known ev en though the mechanism has not been established, In this study, we ha ve used a novel model system to test whether removal of lipoprotein ch olesterol from a localized depot will be affected by apolipoprotein A- I (ape A-I) deficiency, We compared the egress of cholesterol injected in the form of cationized low density lipoprotein into the rectus fem oris muscle of apo A-I K-O and control mice, When the injected lipopro tein had been labeled with [H-3]cholesterol, the t1/2 of labeled chole sterol loss from the muscle was about 4 days in controls and more than 7 days in apo A-I K-O mice, The loss of cholesterol mass had an initi al slow (about 4 days) and a later more rapid component; after day 4, the disappearance curves for apo A-I K-O and controls began to diverge , and by day 7, the loss of injected cholesterol was significantly slo wer in apo A-I K-O than in controls, The injected lipoprotein choleste rol is about 70% in esterified form and undergoes hydrolysis, which by day 4 was similar in control and apo A-I K-O mice, The efflux potenti al of serum from control and apo A-I K-O mice was studied using media containing 2% native or delipidated serum, A significantly lower efflu x of [H-3]cholesterol from macrophages was found with native and delip idated serum from apo A-I K-O mice. In conclusion, these findings show that lack of apo A-I results in a delay in cholesterol loss from a lo calized depot in vivo and from macrophages in culture, These results p rovide support for the thesis that anti-atherogenicity of high density lipoprotein is related in part to its role in cholesterol removal.