Lipoprotein-proteoglycan complexes from atherosclerotic lesions promote cholesteryl ester accumulation in human monocytes/macrophages. Arteriosclerosis Thromb

We studied the metabolism of lipoprotein-proteoglycan com-plexes by macrophage-derived foam cells. Foam cells were iso-lated from atherosclerotic rabbit aortas. ApoB-lipoprotein-proteoglycan complex was isolated from human aorta fibrous plaque lesions and LDL-proteoglycan complex was formed in vitro. Both in vitro and in vivo complexes stimulated choles-teryl ester synthesis in foam cells by a dose-dependent, satura-ble process that resulted in the intracellular accumulation of cholesteryl ester. Stimulation ofcholesteryl ester synthesis was linear with time over a 32-h period. Polyinosinic acid inhibited the stimulation of cholesteryl ester synthesis by the complexes by 32-37%, whereas cytochalasin D only produced a 6-16% inhibition. Foam cells degraded '25I-LDL-proteoglycan com-plex and 125I-acetyl LDL in a saturable, dose-dependent man-ner. Excess unlabeled acetyl-LDL inhibited the degradation of '251-LDL-proteoglycan complex by 52%, while LDL had no effect. Similarly, excess unlabeled complex suppressed the deg-radation of '251-acetyl-LDL by 48%. Foam cells degraded 1251. methyl-LDL-proteoglycan complex to the same extent as 1251_ LDL-proteoglycan complex. These results show that foam cells from atherosclerotic lesions metabolize lipoprotein-pro-teoglycan complexes predominantly via receptor-mediated en-docytosis and consequently continue to accumulate intracellu-lar cholesteryl ester. (J. Clin. Invest. 1993. 91:1011-1018.) Key words: rabbit aorta foam cells * lipoprotein-proteoglycan complex uptake * cholesteryl ester accumulation * receptor pathway * atherosclerosi