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Updated: Mar 9, 2026

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
Altered leukocyte distribution under hypercholesterolemia: A cross-sectional study in children with familial
Jacob J Christensen1, Liv T Osnes2, Bente Halvorsen3
1Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O box 1046, Blindern, 0317 Oslo, Norway; The Lipid Clinic, Oslo University Hospital Rikshospitalet, P.O box 4950, Nydalen, 0424 Oslo, Norway.
Insights
Children with familial hypercholesterolemia (FH) show altered monocyte subpopulations, indicating early-stage atherosclerosis. These changes, particularly in those with low HDL cholesterol, suggest monocyte activation in young FH patients.
Area of Science:
- Immunology
- Cardiovascular Science
- Pediatrics
Background:
- Familial hypercholesterolemia (FH) in children leads to early LDL cholesterol elevation and atherosclerosis.
- Adult FH patients exhibit pro-inflammatory monocyte phenotypes, but this is unstudied in children.
- Lymphocyte subpopulation data in FH children is lacking.
Purpose of the Study:
- To characterize monocyte and lymphocyte subpopulations in children with FH.
- To compare these subpopulations with healthy children.
- To investigate early signs of atherosclerosis in FH children.
Main Methods:
- Flow cytometry was used to analyze B- and T-cell and monocyte subpopulations.
- Whole blood samples from FH (n=23) and healthy (n=20) children were analyzed.
- Serum markers of leukocyte and endothelial cell activation were measured via EIA.
Main Results:
- FH children displayed monocytosis and a shift in monocyte subpopulations.
- Pro-inflammatory and non-classical monocytes were elevated, while classical monocytes were reduced in FH children.
- Monocyte changes and elevated CD18/serum E-selectin were prominent in FH children with low HDL cholesterol.
Conclusions:
- FH children with low HDL cholesterol exhibit monocytosis and a pro-inflammatory monocyte shift.
- Results suggest monocyte activation occurs at a very early stage of atherosclerosis in humans.
- This highlights potential early therapeutic targets in pediatric FH.
Background And Aims:
Children with familial hypercholesterolemia (FH) have elevated LDL cholesterol from the first year of life, and represent a model of early-stage atherosclerosis. Data suggest that adults with FH have alterations in circulating monocyte subpopulations towards a more pro-inflammatory phenotype, but it is not known whether FH children have similar perturbations. In addition, there are no data on the distribution of lymphocyte subpopulations in FH children. The objective of the present study was to characterize the distributions of circulating monocyte and lymphocyte subpopulations in children with FH and healthy, normocholesterolemic children.
Methods:
Using flow cytometry analysis, we analyzed whole blood B- and T-cell subpopulations and monocyte subpopulations in FH (n = 23) and healthy (n = 20) children. Moreover, we measured serum markers of leukocyte and endothelial cell activation using EIA.
Results:
We found that FH children had monocytosis as well as a shift in the monocyte subpopulations. This shift was characterized by higher circulating pro-inflammatory and non-classical monocytes, and lower levels of classical monocytes, and seemed to be present only in FH children with low HDL cholesterol (HDL-C, below 1.3 mmol/L). Additionally, monocytes expressing CD18 and serum E-selectin were higher in FH children, in particular FH children with low HDL-C.
Conclusions:
FH children with low HDL-C had monocytosis as well as a shift in monocyte subpopulations towards a more pro-inflammatory phenotype. Our results suggest activation of monocytes at a very early stage of atherosclerosis in humans.
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