Abnormal high density lipoproteins from patients with liver disease regulate cholesterol metabolism in cultured human skin fibroblasts.
Apolipoprotein B (apoB) of plasma low density lipoproteins (LDL) binds to high affinity receptors on many cell types. A minor subclass of high density lipoproteins (HDL), termed HDL1, which contains apoE but lacks apoB, binds to the same receptor. Bound lipoproteins are engulfed, degraded, and regulate intracellular cholesterol metabolism and receptor activity. The HDL of many patients with liver disease is rich in apoE. We tested the hypothesis that such patient HDL would reduce LDL binding and would themselves regulate cellular cholesterol metabolism. Normal HDL had little effect on binding, uptake, and degradation of 125I-labeled LDL by cultured human skin fibroblasts. Patient HDL (d 1.063-1.21 g/ml) inhibited these processes, and in 15 of the 25 samples studied there was more than 50% inhibition at 125I-labeled LDL and HDL protein concentrations of 10 micrograms/ml and 25 micrograms/ml, respectively. There was a significant negative correlation between the percentage of 125I-labeled LDL bound and the apoE content of the competing HDL (r = -0.54, P less than 0.01). Patient 125I-labeled HDL was also taken up and degraded by the fibroblasts, apparently through the LDL-receptor pathway, stimulated cellular cholesterol esterification, increased cell cholesteryl ester content, and suppressed cholesterol synthesis and receptor activity. We conclude that LDL catabolism by the receptor-mediated pathway may be impaired in liver disease and that patient HDL may deliver cholesterol to cells.
D000328:Adult; D000368:Aged; D001667:Binding, Competitive; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000378:metabolism; D006521:Hepatitis, Chronic / Q000378:metabolism; D006801:Humans; D007525:Isoelectric Focusing; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013395:Sucrose / Q000378:metabolism
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D013395:Sucrose; D002784:Cholesterol