Effect of elevated glucose on gene expression during foam cell formation.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201105 | GEO | 2023/04/20
REPOSITORIES: GEO
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Project description:Background: Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, the differentially expressed proteins were identified. Methods: In this paper, human monocytes, macrophage colony-stimulating factor induced macrophages, and oxidized low-density lipoprotein induced foam cells were cultured, and tandem mass tag (TMT) labeling combined with mass spectrometry (MS) were performed to find associations between foam cell transformation and proteome profiles. Results: Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively, using a cutoff of 1.5-fold change. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus and upregulated DEPs of foam cells/macrophages mostly located in the plasma membrane and extracellular. Functional analysis of DEPs demonstrated that cholesterol metabolism related proteins were upregulated in foam cells, whereas the immune response-related proteins were downregulated in foam cells. The protein-interaction network showed that the DEPs with the highest interaction intensity between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum. Conclusions: This study for the first time to perform quantitative proteomic investigation by TMT labeling and LC-MS/MS to identify differentially expressed proteins in human monocyte, macrophage, and foam cell. The results confirmed cholesterol metabolism was upregulated in foam cells, while immune response was suppressed, which suggested that foam cells were not the population that promote inflammation. In addition, KEGG enrichment analysis and protein-protein interaction indicated that the differentially expressed proteins locating in the endoplasmic reticulum and lysosomes may be key targets to regulate foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism involved in the transformation of macrophages to foam cells.
2022-02-15 | PXD028363 | Pride
Project description:The phagocytosis of oxidized low-density lipoprotein (oxLDL) by monocyte-derived macrophages and the subsequent differentiation of macrophages into foam cells are the key steps in atherogenesis. Our study provides a potential new therapeutic strategy to alleviate oxLDL accumulation and foam cell formation.
2017-12-01 | GSE107522 | GEO
Project description:By identifying differentially expressed LncRNAs/mRNAs in THP-1 macrophages and THP-1 macrophage-derived foam cells, we select some differentially expressed LncRNAs and explore their roles in atherosclerosis process. We already find that some LncRNA can effect cholesterol metabolism and level of inflammation factor, which may influence atherosclerosis process.
2014-05-20 | GSE54039 | GEO
Project description:By identifying differentially expressed LncRNAs/mRNAs in THP-1 macrophages and THP-1 macrophage-derived foam cells, we select some differentially expressed LncRNAs and explore their roles in atherosclerosis process. We already find that some LncRNA can effect cholesterol metabolism and level of inflammation factor, which may influence atherosclerosis process. In the study presented here, 6 human samples were used to acquire expression profiles, which provide futher insight into the pathologies of atherosclerosis
2014-05-20 | E-GEOD-54039 | biostudies-arrayexpress
Project description:The aim of the experiment was to determine the effects of 48 hours of treatment with oxidized low density lipoprotein (oxLDL) on gene expression in primary human monocyte-derived macrophages. 6 independent biological replicates were processed. From each replicate half of the cells were treated with oxLDL and the other half were treated with the control buffer. For foam cell formation (after 7 days) macrophages were treated with oxLDL (50mcg/ml, enodtoxin free, Copper oxidized). Control macrophages were treated with a matching buffer without oxLDL. Treatment duration - 48 hours.
2015-04-08 | E-GEOD-54666 | biostudies-arrayexpress
Project description:Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipid-loaded macrophages in the arterial wall. Intimal macrophages internalize modified lipoproteins such as oxidized LDL (oxLDL) through scavenger receptors, leading to storage of excess cholesteryl esters in lipid bodies and a "foam cell" phenotype. In addition, stimulation of macrophage Toll-like receptors (TLRs) has been shown to promote lipid body proliferation. We investigated the possibility that there are transcriptional regulators that are common to both pathways for stimulating foam cell formation (modified lipoproteins and TLR stimulation), and identified the transcription factor ATF3 as a candidate regulator. In this specific microarray experiment, we studied the effect of genetic knockout of ATF3 on the transcriptional response of macrophages to oxLDL. Murine bone marrow-derived macrophages from two different mouse strains (Atf3-/- and WT) were incubated in the presence or absence of oxidized low-density lipoprotein (oxLDL), and then transcriptionally profiled using the Affymetrix Mouse Exon Array 1.0 ST. The goal was to study the pattern of differential expression between WT and Atf3-/- strains, in oxLDL-induced foam cells and in non-foamy control cells, to identify cellular pathways that may be dysregulated under loss of the transcription factor ATF3 in macrophage foam cells.
2012-03-23 | GSE32358 | GEO
Project description:We report the enhancer landscape in primary human macrophages and foam cells using ChIP-seq for the H3K27ac histone mark CD14+ monocytes were isolated from the blood of 2 healthy male volunteers. Monocytes were differentiated into macrophages by culture for 7 days with 50ng/ml macrophage colony stimulating factor and then treated for 48 hours with either oxidized low density lipoprotein (oxLDL) to induce foam cell formation or with a control buffer that lacked oxLDL. The resulting 4 samples were then subjected to ChIP-seq for H3K27ac.
2015-04-08 | E-GEOD-54972 | biostudies-arrayexpress
Project description:Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipid-loaded macrophages in the arterial wall. Intimal macrophages internalize modified lipoproteins such as oxidized LDL (oxLDL) through scavenger receptors, leading to storage of excess cholesteryl esters in lipid bodies and a "foam cell" phenotype. In addition, stimulation of macrophage Toll-like receptors (TLRs) has been shown to promote lipid body proliferation. We investigated the possibility that there are transcriptional regulators that are common to both pathways for stimulating foam cell formation (modified lipoproteins and TLR stimulation), and identified the transcription factor ATF3 as a candidate regulator. In this specific microarray experiment, we studied the effect of genetic knockout of ATF3 on the transcriptional response of macrophages to oxLDL. Murine bone marrow-derived macrophages from two different mouse strains (Atf3-/- and WT) were incubated in the presence or absence of oxidized low-density lipoprotein (oxLDL), and then transcriptionally profiled using the Affymetrix Mouse Exon Array 1.0 ST. The goal was to study the pattern of differential expression between WT and Atf3-/- strains, in oxLDL-induced foam cells and in non-foamy control cells, to identify cellular pathways that may be dysregulated under loss of the transcription factor ATF3 in macrophage foam cells. Twelve female mice (six Atf3-/-, and six WT control mice) were sacrificed at 8-12 weeks of age, and macrophages were derived from the femoral bone marrow using rhM-CSF. oxLDL was introduced into the medium for six samples (3 WT and 3 Atf3-/-) at 25 ug/mL on day seven, and after 24 h of incubation, RNA was isolated using Trizol. Labeled cRNA derived from the RNA samples was hybridized to Affymetrix Mouse Exon Array 1.0 ST GeneChips. Microarray data were processed using transcript-level probesets, and are in log2 scale.
2012-03-23 | E-GEOD-32358 | biostudies-arrayexpress
Project description:We report the open chromatin landscape in primary human macrophages and foam cells using FAIRE-seq CD14+ monocytes were isolated from the blood of 3 healthy volunteers. Monocytes were differentiated into macrophages by culture for 7 days with 50ng/ml macrophage colony stimulating factor and then treated for 48 hours with either oxidized low density lipoprotein (oxLDL) to induce foam cell formation or with a control buffer that lacked oxLDL. The resulting six samples were then subjected to FAIRE-seq using an established protocol (Simon JM, Giresi PG, Davis IJ, Lieb JD. Using formaldehyde-assisted isolation of regulatory elements (FAIRE) to isolate active regulatory DNA. Nature protocols 2012;7:256-67).
2015-04-08 | E-GEOD-54971 | biostudies-arrayexpress
Project description:Macrophage death in advanced atherosclerotic lesions is a key event in the conversion of benign lesions to vulnerable plaques. One fundamental transcription factor that has been shown to play a pivotal role in cell death/survival is nuclear factor kB (NF-kB). Still, the relevance of this key transcription factor for macrophage-derived foam cell survival has not been unequivocally resolved at the molecular level. THP-1 monocytic cell lines were generated in which NF-kB activation is specifically inhibited by overexpression of a trans-dominant, non-degradable form of IkBa (IkBa (32A/36A)) under control of the macrophage-specific SR-A promoter. A diminished lipid loading during NF-κB inhibition during foam cell formation was accompanied by increased cell death. A genome-wide expression profile of NF-kB-dependent genes during foam cell formation was established showing a widespread effect on the macrophage transcriptome. The three largest functional gene clusters identified and validated by independent techniques, were those involved in lipid metabolism, apoptosis and oxidative stress. The net result of these complex gene expression changes invoked by inhibition of NF-κB activation during lipid loading is a reduction of foam cell survival through caspase-dependent apoptosis. Thus, the NF-kB-dependent gene repertoire seems essential for sustained macrophage survival during the process of pathological lipid loading. Keywords: genetic modification, lipid loading, timecourse THP-1 cells and two different THP-1 IkB mutants (A3 and A12) were exposed to PMA to induce macrophage differentiation and subsequently loaded with oxidized LDL or vehicle for 5 or 8 days. One replicate per array, a total of 15 arrays. A common reference pool, composed of an equimolar mixture of all samples, was labeled with Cy3 and hybridized against the Cy5-labeled experimental sample.
2010-06-24 | E-GEOD-12434 | biostudies-arrayexpress