Gene Expression in early and advanced atherosclerotic plaque from human carotid
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE28829 | GEO | 2011/04/25
SECONDARY ACCESSION(S): PRJNA138791
REPOSITORIES: GEO
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Project description:The objective of this study is to identify genes and pathways involved in the progression of atherosclerotic plaques from early to advanced stage in humans. Samples from atherosclerotic carotid artery segments, from early ((pathological) intimal thickening and intimal xanthoma) and from advanced (thin or thick fibrous cap atheroma) lesions, have been retrieved from the Maastricht Pathology Tissue Collection (MPTC). Tissue was obtained during autopsy (Dept of Pathology, Maastricht University Medical Centre). Collection, storage in the Maastricht Pathology Tissue Collection (MPTC) and use of tissue and patient data were performed in agreement with the "Code for Proper Secondary Use of Human Tissue"
2011-04-25 | E-GEOD-28829 | biostudies-arrayexpress
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:To characterize atherosclerotic plaque cells we isolated cells from the body of vulnerable and stable human atherosclerotic plaques and performed RNA-Seq gene expression profiling of obtained samples.
2018-06-26 | GSE116243 | GEO
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.
2011-10-01 | GSE24495 | GEO
Project description:The rupture of unstable atherosclerotic plaques, leading to debilitating or fatal thrombotic events, is a major health burden worldwide. Limited understanding as to the molecular drivers of plaque instability and rupture hinders efforts in diagnosis and treatment prior to thrombotic events. Utilising an advanced pre-clinical mouse model (Tandem stenosis (TS) model), which presents human-like unstable atherosclerotic disease, we apply high-end omic methods to characterize the molecular signatures associated with plaque instability in atherosclerotic arteries. Through quantitative proteomic profiling, we depict unique proteome signatures of unstable plaques compared to stable plaques and healthy arteries. Coupled with single-cell RNA-sequencing of leukocytes, we describe the heterodimer complex S100a8/S100a9 as unique to unstable plaque, with neutrophils implicated as the transcriptional drivers of S100a8/a9 expression. We confirm S100a9 expression in human carotid atherosclerotic plaques and we further utilise the TS pre-clinical model to pharmacologically inhibit S100a8/S100a9, resulting in plaque stabilisation. Thus, we establish the TS model as a sophisticated translational tool for the profiling of unstable atherosclerotic plaques and demonstrate that unstable and stable atherosclerosis are highly different disease entities.
2023-05-10 | PXD030857 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE23303: Gene expression profiling of human atherosclerotic plaque: Laser capture microscopy of smooth muscle cells and macrophages GSE23304: Gene expression profiling of human atherosclerotic plaque: 101 peripheral plaques GSE24495: Gene expression profiling of human atherosclerotic plaque: Carotid plaque GSE24702: Gene expression profiling of human atherosclerotic plaque: 290 peripheral plaques Refer to individual Series
2011-09-30 | E-GEOD-23314 | biostudies-arrayexpress
Project description:The rupture of unstable atherosclerotic plaques, leading to debilitating or fatal thrombotic events, are a major health concern worldwide. Limited understanding as to the molecular drivers of plaque destabilisation and rupture hinders efforts in diagnosis and treatment prior to thrombotic events. Using an advanced pre-clinical model (tandem stenosis), we characterise the molecular signatures associated with plaque instability in atherosclerotic vessels.
2023-07-24 | PXD018224 | Pride
Project description:Aberrantly expressed miRNAs contribute to developmental abnormalities and diseases such as cancer, diabetes, and cardiovascular disorders, by hybridizing to specific mRNA targets and repressing their translation into proteins. Although miRNA expression signature is characterized in the process of neointimal thickening during proliferative vascular diseases such as atherosclerosis, so far global miRNA expression profiling in the different stages of atherosclerosis is completely unknown. We explored stage-specific microRNA signatures in the progress of atherosclerosis in hyperlipidemia mouse model, which may help to identify the critical miRNAs contributing atherosclerotic development and stabilization.
2013-03-27 | GSE34647 | GEO
Project description:Aberrantly expressed miRNAs contribute to developmental abnormalities and diseases such as cancer, diabetes, and cardiovascular disorders, by hybridizing to specific mRNA targets and repressing their translation into proteins. Although miRNA expression signature is characterized in the process of neointimal thickening during proliferative vascular diseases such as atherosclerosis, so far global miRNA expression profiling in the different stages of atherosclerosis is completely unknown. We explored stage-specific microRNA signatures in the progress of atherosclerosis in hyperlipidemia mouse model, which may help to identify the critical miRNAs contributing atherosclerotic development and stabilization. Female apoe-/- mice (6-8 weeks, Jackson Laboratory) were fed a high fat diet (HFD, 21% crude fat, 0.15% cholesterol and 19.5% casein, Altromin, Germany) for 3 or 10 months (N=3-4). Serial sections (20 µm thick) of aortic roots and carotid arteries from these mice were mounted on membrane mounted metal frame slides (MMI), deparaffinized under RNase-free conditions, and completely dried. Laser capture microdissection (LCM) was performed with a laser microdissection system (MMI cellcut plus, Molecular Machines and Industries, Switzerland) assembled onto an inverted microscope (Olympus IX71). Plaque tissue or morphologically normal vessel wall of at least 40 sections per mouse were collected. RNA was isolated using RecoverAll total nucleic acid isolation kit (Applied Biosystems) according to the manufacturer’s instructions.
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