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Using circulating mononuclear cells as a readily available tissue and using the rate of high affinity degradation of 125-I-labeled low density lipoprotein (LDL) as an index of cell surface LDL receptor activity, we have measured receptor activity in cells from 53 individuals. This group includes 32 healthy subjects, 15 subjects with the heterozygous form of familial hypercholesterolemia, and 6 subjects with hyperlipidemic disorders other than familial hypercholesterolemia. 7 of the healthy subjects and 10 of the heterozygotes were members of a single large kindred with five-generation transmission of the mutant familial hypercholesterolemia gene. LDL receptor activity was assayed in blood mononuclear cells under two sets of conditions. First, 125I-LDL degradation was measured in purified lymphocytes that had been incubated for 3 days in the absence of lipoproteins so as to induce a high level of LDL receptor activity. Phase-contrast autoradiograms of cells incubated with 125I-LDL and electron micrographs of cells incubated with ferritin-labeled LDL confirmed the existence of LDL receptors on lymphocytes. Second, 125I-LDL degradation was measured in mixed mononuclear cells (85-90% lymphocytes and 5-15% monocytes) immediately after their isolation from the bloodstream. This assay represented an attempt to assess the number of receptors actually expressed on the cells when they were in the circulation. Under both sets of conditions, cells from the familial hypercholesterolemia heterozygotes expressed an average of about one-half the normal number of LDL receptors. The current findings are consistent with the conclusion that heterozygotes with familial hypercholesterolemia possess only one functional allele at the LDL receptor locus and that the consequent deficiency of LDL receptors produces the clinical syndrome of heterozygous familial hypercholesterolemia.


D W Bilheimer, Y K Ho, M S Brown, R G Anderson, J L Goldstein


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Citations to this article in year 1993 (4)

Title and authors Publication Year
The effects of hypercholesterolaemia, simvastatin and dietary fat on the low density lipoprotein receptor of unstimulated mononuclear cells
PD Roach, J Hosking, PM Clifton, R Bais, B Kusenic, P Coyle, MB Wight, DW Thomas, PJ Nestel
Atherosclerosis 1993
Coordinate changes in the low density lipoprotein receptor activity of liver and mononuclear cells in the rabbit
PD Roach, NL Kerry, MJ Whiting, PJ Nestel
Atherosclerosis 1993
Non-steady-state kinetics of low density lipoproteins in man: studies after plasma exchange in healthy subjects and patients with familial hypercholesterolaemia
M Eriksson, L Berglund, J Gabrielsson, B Lantz, B Angelin
European Journal of Clinical Investigation 1993
Hypo- and Hyperresponse of Serum Cholesterol Level and Low Density Lipoprotein Production and Degradation to Dietary Cholesterol in Man
JF Glatz, PR Turner, MA KATANf, AF Stalenhoef, B Lewis
Annals of the New York Academy of Sciences 1993