Transcriptome analysis reveals non-foamy rather than foamy plaque macrophages are pro-inflammatory in atherosclerotic murine models
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ABSTRACT:
PROVIDER: PRJNA477941 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR7425020.fastq.gz | Fastqsanger.gz | |||
| SRR7425021.fastq.gz | Fastqsanger.gz | |||
| SRR7425022.fastq.gz | Fastqsanger.gz | |||
| SRR7425017.fastq.gz | Fastqsanger.gz |
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2023-05-10 | PXD030857 | Pride
Project description:In order to identify potential new biomarkers of atherosclerotic plaque composition we performed a large scale analysis of gene expression patterns in human atherosclerotic lesions. Whole genome expression analysis of 101 peripheral plaques identified a robust gene signature (1514 genes) dominated by inflammatory processes, and cholesterol metabolism and storage genes. Specific pathways enriched in this signature included activation of the Toll-like receptor signaling pathway, T-cell activation, cholesterol efflux, oxidative stress response, inflammatory cytokine production, vasoconstriction and lysosomal activity. Analysis of gene expression in plaque micro-dissected material revealed that the signature is strongly up-regulated in macrophage-rich regions and down-regulated in regions with high smooth muscle cell content. A smaller qPCR biomarker panel and inflammatory composite score (ICS) were developed to facilitate clinical translation of discoveries from gene expression profiling. We found that ICS correlates with histological features related to plaque vulnerability. In addition, ICS is able to separate groups of plaques obtained from symptomatic and asymptomatic patients undergoing carotid endarerectomy. In summary, we identified a robust mRNA biomarker panel associated with histo-pathological as well as clinical hallmarks of vulnerable atherosclerotic plaque. This panel may be used as a diagnostic and prognostic tool in clinical setting to evaluate novel anti-atherosclerotic therapies. 6 human carotid plaques were sectioned in 1 mm thick slices. Alternative slices were used for gene expression profiling in Affymetrix/Merck custom 1.0 arrays (GPL10687), or for immunohistochemistry studies (CD68, Actin)
2011-09-30 | E-GEOD-24495 | biostudies-arrayexpress
Project description:Macrophages in atherosclerotic aorta are major population in lesion and contributes to lesion formation by becoming foam cells. To investigate in vivo transcriptome profiles of those macrophages, we extracted foamy and non-foamy macrophages from atherosclerotic aorta using lipid probe-based flow cytometry sorting. Our data indicates that intima non-foamy and foamy macrophages show different mRNA expressions. Rather than non-foamy macrophages, foamy macrophages expressed more genes related to cholesterol metabolism, oxidative phosphorylation, lysosome and so on. The non-foamy macrophages expressed more genes related to immune response (Il-1b related pathways, TNF, TLR signaling pathways) than foamy macrophages.
2018-08-30 | GSE116239 | GEO
Project description:Atherosclerosis is a chronic inflammatory disease of the blood vessels, characterized by atherosclerotic lesions. Early vascular injury initiates excessive inflammatory and immune responses, communicated by blood leukocytes and cells from the vasculature. Key factors contributing to early stages of atherosclerosis and plaque development include the pro-inflammatory cytokine IFNγ, which is vital for both innate and adaptive immunity and is also expressed at high levels in atherosclerotic lesions. Recent discoveries provide novel evidence to suggest that IFNγ-activated STAT1 orchestrates a platform of cell-type common and specific inflammatory responses in Vascular Smooth Muscle Cells (VSMC) and macrophages (MΦ) that are instrumental in the onset and progression of atherosclerotic plaque formation. Therefore, we compared genome-wide transcriptional responses of mouse VSMCs and bone marrow-derived macrophages (BMDMs) in time-dependent IFNγ response using RNA-seq. We identified genes upregulated both in a common and cell-type-specific manner. Next, comparative analysis with RNAseq data from aortic plaques from HFD-treated ApoEKO mice identified 225 differentially expressed genes with a BMDM-specific character. These included many known IFNγ target genes containing putative GAS and ISRE sites in their promoters. Likewise, using a scRNAseq data set obtained from human coronary atherosclerotic plaques, identified 98 pro-inflammatory and pro-atherogenic genes that were characterized as BMDM-specific and exclusively expressed in foamy, inflammatory, monocytes and tissue-resident BMDM subtypes. Finally, we identified a 25 BMDM-specific gene subset commonly expressed in mouse and human plaques, over-representing STAT1-binding sites and predominantly associated with Leukocyte Chemotaxis and Migration. These results provide strong evidence for a BMDM-specific role of STAT1 in coronary artery plaque development and identify a BMDM-specific STAT1-dependent pro-inflammatory gene signature that could serve to monitor and diagnose plaque progression in human atherosclerosis.
2024-09-09 | GSE276417 | GEO
Project description:Atherosclerosis is a chronic inflammatory disease of the blood vessels, characterized by atherosclerotic lesions. Early vascular injury initiates excessive inflammatory and immune responses, communicated by blood leukocytes and cells from the vasculature. Key factors contributing to early stages of atherosclerosis and plaque development include the pro-inflammatory cytokine IFNγ, which is vital for both innate and adaptive immunity and is also expressed at high levels in atherosclerotic lesions. Recent discoveries provide novel evidence to suggest that IFNγ-activated STAT1 orchestrates a platform of cell-type common and specific inflammatory responses in Vascular Smooth Muscle Cells (VSMC) and macrophages (MΦ) that are instrumental in the onset and progression of atherosclerotic plaque formation. Therefore, we compared genome-wide transcriptional responses of mouse VSMCs and bone marrow-derived macrophages (BMDMs) in time-dependent IFNγ response using RNA-seq. We identified genes upregulated both in a common and cell-type-specific manner. Next, comparative analysis with RNAseq data from aortic plaques from HFD-treated ApoEKO mice identified 225 differentially expressed genes with a BMDM-specific character. These included many known IFNγ target genes containing putative GAS and ISRE sites in their promoters. Likewise, using a scRNAseq data set obtained from human coronary atherosclerotic plaques, identified 98 pro-inflammatory and pro-atherogenic genes that were characterized as BMDM-specific and exclusively expressed in foamy, inflammatory, monocytes and tissue-resident BMDM subtypes. Finally, we identified a 25 BMDM-specific gene subset commonly expressed in mouse and human plaques, over-representing STAT1-binding sites and predominantly associated with Leukocyte Chemotaxis and Migration. These results provide strong evidence for a BMDM-specific role of STAT1 in coronary artery plaque development and identify a BMDM-specific STAT1-dependent pro-inflammatory gene signature that could serve to monitor and diagnose plaque progression in human atherosclerosis.
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Project description:In order to identify potential new biomarkers of atherosclerotic plaque composition we performed a large scale analysis of gene expression patterns in human atherosclerotic lesions. Whole genome expression analysis of 101 peripheral plaques identified a robust gene signature (1514 genes) dominated by inflammatory processes, and cholesterol metabolism and storage genes. Specific pathways enriched in this signature included activation of the Toll-like receptor signaling pathway, T-cell activation, cholesterol efflux, oxidative stress response, inflammatory cytokine production, vasoconstriction and lysosomal activity. Analysis of gene expression in plaque micro-dissected material revealed that the signature is strongly up-regulated in macrophage-rich regions and down-regulated in regions with high smooth muscle cell content. A smaller qPCR biomarker panel and inflammatory composite score (ICS) were developed to facilitate clinical translation of discoveries from gene expression profiling. We found that ICS correlates with histological features related to plaque vulnerability. In addition, ICS is able to separate groups of plaques obtained from symptomatic and asymptomatic patients undergoing carotid endarerectomy. In summary, we identified a robust mRNA biomarker panel associated with histo-pathological as well as clinical hallmarks of vulnerable atherosclerotic plaque. This panel may be used as a diagnostic and prognostic tool in clinical setting to evaluate novel anti-atherosclerotic therapies.
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Project description:Formation of foam cell macrophages (FCMs), which sequester extracellular modified lipids, is a key event in atherosclerosis. How lipid loading affects macrophage phenotype is controversial, with evidence suggesting either pro- or anti-inflammatory consequences. To investigate this further, we compared the transcriptomes of foamy and non-foamy macrophages (NFMs) that accumulate in the subcutaneous granulomas of fed-fat ApoE null mice and normal chow fed wild-type mice in vivo. Consistent with previous studies, LXR/RXR pathway genes were significantly over-represented among the genes up-regulated in foam cell macrophages. Unexpectedly, the hepatic fibrosis pathway, associated with platelet derived growth factor and transforming growth factor-? action, was also over-represented. Several collagen polypeptides and proteoglycan core proteins as well as connective tissue growth factor and fibrosis-related FOS and JUN transcription factors were up-regulated in foam cell macrophages. Increased expression of several of these genes was confirmed at the protein level in foam cell macrophages from subcutaneous granulomas and in atherosclerotic plaques. Moreover, phosphorylation and nuclear translocation of SMAD2, which is downstream of several transforming growth factor-? family members, was also detected in foam cell macrophages. We conclude that foam cell formation in vivo leads to a pro-fibrotic macrophage phenotype, which could contribute to plaque stability, especially in early lesions that have few vascular smooth muscle cells. Samples (n=4/group): Foam cell macrophages (FCM) isolated from inflammatory sponges placed in ApoE null mice fed a high-fat diet (n=4), non-foamy macrophages (NFM) isolated from inflammatory sponges placed in control mice fed a normal diet (n=4).
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