Stimulation of cholesteryl ester synthesis in macrophages by extracts of atherosclerotic human aortas and complexes of albumin/cholesteryl esters.
Cholesteryl ester-rich particles extracted from human atherosclerotic plaques were shown to increase the rate of incorporation of [14C]oleate into cholesteryl [14C]oleate and to cause massive accumulation of cholesteryl esters in monolayers of mouse peritoneal macrophages. This stimulation showed saturation kinetics and susceptibility to competition by polyanions (polyinosinic acid, fucoidin, dextran sulfate), suggesting that cell surface binding was required. Cellular uptake and lysosomal hydrolysis of the cholesteryl esters were also required, as indicated by the finding that stimulation of cholesteryl ester formation was prevented by the lysosomal inhibitor, chloroquine. The cholesterol esterification-stimulating activity of the aortic extracts was excluded on a 2% agarose column and floated in the density range of 1.006 to 1.063 g/ml. Cholesterol-rich extracts from human adrenal glands and liver did not stimulate cholesteryl ester formation in macrophages. The aortic extracts did not stimulate cholesteryl ester synthesis in human fibroblasts. Complexes of 125I-labeled albumin and cholesteryl linoleate formed in vitro were taken up and degraded in macrophages, but not in fibroblasts, by a process resembling the uptake of the aortic extracts. The current data suggest that macrophages express mechanisms for internalizing certain types of cholesteryl ester-rich lipid/protein complexes, including those present in atherosclerotic plaques.
D000328:Adult; D000368:Aged; D000418:Albumins / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001161:Arteriosclerosis / Q000378:metabolism*; D002788:Cholesterol Esters / Q000096:biosynthesis* / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D014020:Tissue Extracts / Q000494:pharmacology*
D000418:Albumins; D002788:Cholesterol Esters; D014020:Tissue Extracts; C021976:cholesteryl linoleate