Citations to this article


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 1979 (6)

Title and authors Publication Year
Reconstituted low density lipoprotein: A vehicle for the delivery of hydrophobic fluorescent probes to cells
M Krieger, LC Smith, RG Anderson, JL Goldstein, YJ Kao, HJ Pownall, AM Gotto, MS Brown
Journal of Supramolecular Structure 1979
Cellular pathology of homozygous familial hypercholesterolemia
LM Buja, PT Kovanen, DW Bilheimer
The American Journal of Pathology 1979
Metabolic Studies in Familial Hypercholesterolemia EVIDENCE FOR A GENE-DOSAGE EFFECT IN VIVO
DW Bilheimer, NJ Stone, SM Grundy
Journal of Clinical Investigation 1979
Lysosomal association of internalized 125I-insulin in isolated rat hepatocytes. Direct demonstration by quantitative electron microscopic autoradiography
JL Carpentier, P Gorden, P Freychet, AL Cam, L Orci
Journal of Clinical Investigation 1979
Evidence for rate-limiting steps in sterol synthesis beyond 3-hydroxy-3-methylglutaryl-coenzyme a reductase in human leukocytes
CP Burns, IR Welshman, J Edmond, AA Spector
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1979
Proceedings of the 1978 Laurentian Hormone Conference
MS Brown, PT Kovanen, JL Goldstein
Proceedings of the 1978 Laurentian Hormone Conference 1979