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Series GSE6054 Query DataSets for GSE6054
Status Public on Apr 01, 2008
Title Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Background: Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH) with those from healthy individuals.
Methods: Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography ? mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p < 0.05; Benjamini Hochberg correction, False Discovery Rate = 0.05). The differential expression of FH associated genes was validated at the mRNA level by qRT-PCR and/or at the protein level by Western Blot or flow cytometry. Functional validation of monocyte scavenger receptor activities were done by binding assays and dose/time dependent uptake analysis using native and oxidized LDL.
Results: Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells.
Conclusion: Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.

Keywords: Micro-array analysis, cell type comparison,
Overall design 23 monocytes samples: 4 homozygous FH, 6 heterozygous FH, 13 control participants
Contributor(s) Mosig S, Rennert K, Buettner P, Soufi M, Krause S, Kzhyshkowska J, Goerdt S, Heller R, Schaefer JR, Funke H, Kuehn B, Neunuebel K, Schreiner T
Citation(s) 19040724
Submission date Oct 17, 2006
Last update date Mar 25, 2019
Contact name Sandy Mosig
Phone +49-3641-934813
Fax +49-3641-933950
Organization name University Hospital Jena
Department Molecular Hemostaseology - Institute of Vascular Medicine
Street address Bachstrasse 18
City Jena
ZIP/Postal code 07743
Country Germany
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (23)
GSM140232 heterozygot FH P249
GSM140233 homozygot FH P251
GSM140234 homozygot FH P253
BioProject PRJNA97731

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE6054_RAW.tar 180.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file

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