Lipid accumulation in arterial smooth muscle cells in culture. Morphological and biochemical changes caused by low density lipoproteins and chloroquine.
Cultured smooth muscle cells from pig aortas were incubated with low density lipoproteins (LDL) and chloroquine for up to 5 days, as an in vitro model for lipid accumulation in atherosclerosis. Cells incubated with LDL alone had a normal morphology, except that some cells contained large lipid droplets. The activities of acid phosphatase, catalase and malate dehydrogenase were increased in homogenates prepared from these cells. Cells incubated with chloroquine alone developed large autophagic vacuoles. The activities of the three acid hydrolases, acid phosphatase, N-acetyl-beta-glucosaminidase and beta-glucuronidase, were decreased, as was the proteolytic activity of the cell homogenates at acid pH toward 125I-labelled LDL. There was, however, a transient increase in the activity of malate dehydrogenase. Chloroquine by itself was toxic to the cells, but LDL protected against this toxic effect. Cells incubated with LDL and chloroquine together developed both autophagic vacuoles and large lipid droplets. The cholesteryl ester content of the cells was increased many-fold and the non-esterified cholesterol content was increased to a lesser extent. The above four acid hydrolase activities were decreased, as was the activity of catalase, whereas the activities of lactate dehydrogenase and malate dehydrogenase were increased.
D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002738:Chloroquine / Q000032:analysis / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis; D002788:Cholesterol Esters / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D006867:Hydrolases / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D014176:Protein Biosynthesis; D013552:Swine; D014617:Vacuoles / Q000473:pathology / Q000648:ultrastructure
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D002738:Chloroquine; D004247:DNA; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase; D006867:Hydrolases