Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism
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.
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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.
Sample ID | !Sample_title | cell type | disease state |
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GSM140232 | heterozygot FH P249 | monocyte | heterozygote FH |
GSM140233 | homozygot FH P251 | monocyte | homozygote FH |
GSM140234 | homozygot FH P253 | monocyte | homozygote FH |
GSM140235 | homozygot FH P262 | monocyte | homozygote FH |
GSM140236 | heterozygot FH P266 | monocyte | heterozygote FH |
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Sample ID | !Sample Title | Cell type | Disease state |
---|---|---|---|
GSM140232 | heterozygot FH P249 |
monocyte |
heterozygote FH |
GSM140233 | homozygot FH P251 |
monocyte |
homozygote FH |
GSM140234 | homozygot FH P253 |
monocyte |
homozygote FH |
GSM140235 | homozygot FH P262 |
monocyte |
homozygote FH |
GSM140236 | heterozygot FH P266 |
monocyte |
heterozygote FH |
GSM140237 | homozygot FH P270wh |
monocyte |
homozygote FH |
GSM140239 | heterozygot FH P279 |
monocyte |
heterozygote FH |
GSM140240 | heterozygot FH P282 |
monocyte |
heterozygote FH |
GSM140241 | heterozygot FH P560 |
monocyte |
heterozygote FH |
GSM140244 | control participant P303 |
monocyte |
control participant |
GSM140245 | control participant P307 |
monocyte |
control participant |
GSM140246 | control participant P309 |
monocyte |
control participant |
GSM140247 | control participant P311 |
monocyte |
control participant |
GSM140248 | control participant P313 |
monocyte |
control participant |
GSM140249 | control participant P317 |
monocyte |
control participant |
GSM140250 | control participant P319 |
monocyte |
control participant |
GSM140251 | control participant P327 |
monocyte |
control participant |
GSM140252 | control participant P329 |
monocyte |
control participant |
GSM140253 | control participant P331 |
monocyte |
control participant |
GSM140254 | control participant P333 |
monocyte |
control participant |
GSM140255 | control participant P335 |
monocyte |
control participant |
GSM140256 | control participant P351 |
monocyte |
control participant |
GSM140257 | heterozygot FH P387neu |
monocyte |
heterozygote FH |
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