Uptake of chylomicron remnants causes cholesterol accumulation in cultured human arterial smooth muscle cells.
Chylomicron remnants (Sf greater than 100) were prepared by treating human chylomicrons (Sf greater than 400) with human post heparin plasma. Chylomicron remnants recovered after 70-80% of chylomicron triacylglycerol was hydrolyzed, suppressed LDL-receptor activity and increased cell cholesterol esterification to the same extent as did LDL when added to cultured human arterial smooth muscle cells at an equal cholesterol concentration. Cell cholesterol mass increased 36% after incubation with 25 micrograms LDL cholesterol/ml and 35% with 25 micrograms chylomicron-remnant cholesterol/ml. Addition of 30 microM chloroquine plus LDL or chylomicron remnants further increased cholesterol content of cells (74% and 87%, respectively) and caused a significant rise in cell esterified cholesterol (344% and 369%, respectively). Cholesterol content per unit of apolipoprotein B mass of remnants was 2-3-fold higher than that of LDL. Therefore, if lipoprotein particles were added at equivalent apolipoprotein B mass chylomicron remnants increased cell cholesterol content and cholesterol esterification and suppressed LDL receptor activity significantly more than did LDL. This suggests that an additional determinant, presumably apolipoprotein E, is important for receptor recognition of chylomicron remnants. These results may be relevant to the delivery of chylomicron-derived cholesterol to arterial cells proposed as a feature of atherogenesis.
D001013:Aorta, Thoracic / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000096:biosynthesis; D002914:Chylomicrons / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000378:metabolism; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000378:metabolism; D011973:Receptors, LDL
D002788:Cholesterol Esters; D002914:Chylomicrons; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D002784:Cholesterol