Heritability of the Low Density Lipoprotein Receptor Activity of Human Blood Mononuclear Cells: Studies in Normolipidaemic Adult Male Twins

1982 ◽  
Vol 62 (4) ◽  
pp. 397-401 ◽  
Author(s):  
M. Weight ◽  
C. Cortese ◽  
U. Sule N. E. Miller ◽  
B. Lewis
Keyword(s):  
Adult Male ◽  
Mononuclear Cells ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Monozygotic Twins ◽  
Density Lipoprotein ◽  
Correlation Coefficients ◽  
Receptor Activity ◽  
Low Density ◽  
Blood Mononuclear Cells

1. The concordance of low density lipoprotein (LDL) receptor activity of blood mononuclear cells was examined in 26 pairs of monozygotic and 17 pairs of dizygotic normolipidaemic young adult male twins. 2. Receptor activity was quantified as the degradation of 125I-labelled LDL during a 6 h incubation, after derepression of the cells for 72 h in lipoprotein-deficient medium. 3. The total variance of receptor activity was similar in the two groups of twins. In contrast, within-pair variance was five times greater in dizygotic twins than in monozygotic twins (P < 0.001). 4. Estimates of heritability, mostly based on the intra-class correlation coefficients (monozygotic, r = 0.83; dizygotic, r = 0.39), ranged from 0.72 to 1.05. 5. These results suggest that the maximal LDL receptor activity of peripheral cells in normolipidaemic subjects is largely genetically determined.

scholarly journals A study of the chylomicron metabolism in WHHL rabbits after fat loading. Discrepancy between results based on measurement of apoprotein B-48 or retinyl palmitate

1992 ◽  
Vol 285 (2) ◽  
pp. 641-646 ◽  
Author(s):  
P N M Demacker ◽  
P J van Heijst ◽  
A F H Stalenhoef
Keyword(s):  
New Zealand ◽  
Strong Correlation ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Retinyl Palmitate ◽  
Receptor Activity ◽  
Low Density ◽  
Apoprotein B ◽  
Chylomicron Metabolism

We studied the metabolism of chylomicrons in homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits and in cholesterol-fed or normally fed New Zealand White (NZW) rabbits by measuring the concentrations of apoprotein B-48 and of retinyl palmitate in their serum after feeding fat plus this vitamin according to two different protocols. Compared with NZW controls, retinyl palmitate accumulated in both hyperlipidaemic groups under study, not only in the d less than 1.019 fraction but also in the low-density lipoprotein (LDL) fraction. A strong correlation was found between the retinyl palmitate concentration in either the d less than 1.019 fraction or the LDL fraction of the WHHL rabbits and the concentrations of cholesterol and triacylglycerols in these fractions. This suggests that retinyl palmitate is exchanged rapidly between exogenous and endogenous lipoproteins. This is supported by the lack of a correlation between the retinyl palmitate concentrations and the intensity of the apoprotein B-48 band in the respective d less than 1.019 fractions or LDL fractions; in most fractions, in which large amounts of retinyl palmitate were present, the intensity of the apoprotein B-48 band was not increased compared with the fasting concentrations. Assuming that retinyl palmitate is a marker for the transfer of exogenous lipids, the results of our experiments indicate that the removal of exogenous lipids is delayed by complexing to endogenously synthesized lipoproteins. However, the clearance of apoprotein B-48 is normal and thus independent of the LDL-receptor activity.

scholarly journals Immunoprecipitation of the low-density-lipoprotein (LDL) receptor and its precursor from human monocyte-derived macrophages

1986 ◽  
Vol 233 (3) ◽  
pp. 683-690 ◽  
Author(s):  
A K Soutar ◽  
B L Knight
Keyword(s):  
Mononuclear Cells ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Human Monocyte ◽  
Skin Fibroblasts ◽  
Receptor Protein ◽  
Low Density ◽  
Human Mononuclear Cells ◽  
Cell Extracts

Synthesis of the low-density-lipoprotein (LDL) receptor protein by cultured human monocyte-derived macrophages was demonstrated by immunoprecipitation of [35S]methionine-labelled cell extracts with a monoclonal antibody to the bovine adrenal LDL receptor. Although the antibody does not bind to or inhibit binding of 125I-LDL to the LDL receptor on intact fibroblasts, it specifically binds to a protein in extracts of human skin fibroblasts, of Mr approx. 130,000 under non-reducing conditions, that is able to bind LDL. In monocyte-derived macrophages, as in fibroblasts, the receptor is synthesized as a low-Mr precursor that is converted into the mature protein. The half-life of the precursor in human macrophages is approx. 44 min. In cells from two homozygous familial-hypercholesterolaemic subjects, only the precursor form of the receptor is synthesized. Detection of abnormalities of LDL-receptor synthesis in human mononuclear cells may be a useful aid in diagnosis of familial hypercholesterolaemia that is simpler and quicker than methods requiring growth of cultured skin fibroblasts.

scholarly journals Transcriptomic Profiles Reveal Downregulation of Low-Density Lipoprotein Particle Receptor Pathway Activity in Patients Surviving Severe COVID-19

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3495
Author(s):  
Ivan Vlasov ◽  
Alexandra Panteleeva ◽  
Tatiana Usenko ◽  
Mikhael Nikolaev ◽  
Artem Izumchenko ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Transcriptional Response ◽  
Cholesterol Homeostasis ◽  
Receptor Activity ◽  
Low Density ◽  
Peripheral Blood Mononuclear ◽  
Pathway Activity ◽  
Medical University

To assess the biology of the lethal endpoint in patients with SARS-CoV-2 infection, we compared the transcriptional response to the virus in patients who survived or died during severe COVID-19. We applied gene expression profiling to generate transcriptional signatures for peripheral blood mononuclear cells (PBMCs) from patients with SARS-CoV-2 infection at the time when they were placed in the Intensive Care Unit of the Pavlov First State Medical University of St. Petersburg (Russia). Three different bioinformatics approaches to RNA-seq analysis identified a downregulation of three common pathways in survivors compared with nonsurvivors among patients with severe COVID-19, namely, low-density lipoprotein (LDL) particle receptor activity (GO:0005041), important for maintaining cholesterol homeostasis, leukocyte differentiation (GO:0002521), and cargo receptor activity (GO:0038024). Specifically, PBMCs from surviving patients were characterized by reduced expression of PPARG, CD36, STAB1, ITGAV, and ANXA2. Taken together, our findings suggest that LDL particle receptor pathway activity in patients with COVID-19 infection is associated with poor disease prognosis.

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