title: Altered leukocyte distribution under hypercholesterolemia: A cross-sectional study in children with familial hypercholesterolemia.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department 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.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Christensen
authors.affiliation: Department of Immunology, Oslo University Hospital Rikshospitalet, P.O box 4950, Nydalen, 0424 Oslo, Norway.
authors.forename: Liv T
authors.initials: LT
authors.lastname: Osnes
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, P.O box 4950, Nydalen, 0424 Oslo, Norway; Institute of Clinical Medicine, University of Oslo, P.O box 1171, Blindern, 0318 Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, P.O box 1171, Blindern, 0318 Oslo, Norway.
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.affiliation: Department 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.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Retterstøl
authors.affiliation: Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital Rikshospitalet, P.O box 4950, Nydalen, 0424 Oslo, Norway.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Bogsrud
authors.affiliation: The Lipid Clinic, Oslo University Hospital Rikshospitalet, P.O box 4950, Nydalen, 0424 Oslo, Norway.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Wium
authors.affiliation: The Lipid Clinic, Oslo University Hospital Rikshospitalet, P.O box 4950, Nydalen, 0424 Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Svilaas
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O box 1046, Blindern, 0317 Oslo, Norway; Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital Rikshospitalet, P.O box 4950, Nydalen, 0424 Oslo, Norway.
authors.forename: Ingunn
authors.initials: I
authors.lastname: Narverud
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O box 1046, Blindern, 0317 Oslo, Norway.
authors.forename: Stine M
authors.initials: SM
authors.lastname: Ulven
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, P.O box 4950, Nydalen, 0424 Oslo, Norway; Institute of Clinical Medicine, University of Oslo, P.O box 1171, Blindern, 0318 Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, P.O box 1171, Blindern, 0318 Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, P.O box 4950, Nydalen, 0424 Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O box 1046, Blindern, 0317 Oslo, Norway; Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital Rikshospitalet, P.O box 4950, Nydalen, 0424 Oslo, Norway. Electronic address: k.b.holven@medisin.uio.no.
authors.forename: Kirsten B
authors.initials: KB
authors.lastname: Holven
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology*; D010641:Phenotype
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL
keywords: Atherosclerosis; Children; Familial hypercholesterolemia; Inflammation; Lymphocytes; Monocytes