MiRNA expression profiling for human normal arterial intimae and advanced atherosclerotic plaques
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE226791 | GEO | 2023/05/25
REPOSITORIES: GEO
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Project description:To analyze the cause of arterial plaque formation and development, our arteries in patients with normal donors and severe arterial plaques sampling, the transcriptome sequencing, to explore its molecular mechanism.
2023-05-25 | GSE226790 | GEO
Project description:Atherosclerosis is a serious and very common condition where plaque builds up inside arteries and that can lead to heart attack or stroke. The development and rupture of the plaque is a complex process, involving the interplay of many cell types and the extracellular environment. We performed RNAseq on stable and unstable regions dissected from fresh human carotid plaques obtained at carotid endarterectomy in symptomatic patients. The dissection of the plaques into stable and unstable regions was based on macroscopic appearance, with unstable regions characterised as the visible zone of plaque rupture.
2019-08-02 | GSE120521 | 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:Cardiovascular disease (CVD) is the leading cause of death, with atherosclerosis a major underlying cause. While often asymptomatic for decades, plaque destabilisation and rupture can arise suddenly and cause acute arterial occlusion or peripheral embolisation resulting in acute myocardial infarction, stroke and lower limb ischaemia. Hard plaques are typically considered as stable, and soft plaques as unstable. Extracellular matrix (ECM) remodelling can result in plaque destabilisation, but the mechanisms that drive the development of unstable lipid-rich plaques with a thin fibrous cap, versus stable fibrotic plaques with a thick cap, are not fully understood. We hypothesised that there would be significant differences in ECM composition between hard (stable) and soft (unstable and rupture-prone) plaques. We identified and quantified >46700 proteins, including 367 ECM proteins, with unprecedented coverage and high reproducibility. We identified 575 proteins with differential abundances between hard (stable) and soft (unstable) plaques. Proteins involved in inflammation and ECM remodeling, including multiple proteases were enriched, and ECM proteins decreased, in soft plaques. These data provide a unique insight into inflammatory mechanisms and ECM remodelling as an explanation for plaque destabilization. Furthermore they provide a first step towards identifying circulating biomarkers for individualised risk profiling of arteriosclerosis.
2024-01-15 | PXD039077 | 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. Total RNA from peripheral plaque (n=101) profiled in the Merck/Agilent 44k v1.1 against a reference pool of total RNA from 7 carotid plaques.
2011-09-30 | E-GEOD-23304 | 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. 290 human peripheral plaques were excised using the FoxHollow silverhawk catheter and stored in RNAlater. RNA was extracted, amplified and hybridized to Affymetrix/Merck custom 1.0 arrays (GPL10687).
2011-09-30 | E-GEOD-24702 | biostudies-arrayexpress
Project description:Using single-cell proteomic and transcriptomic analyses, we uncovered distinct features of both T cells and macrophages in carotid artery plaques of patients with clinically symptomatic disease (recent stroke or transient ischemic attack) compared to asymptomatic disease (no recent stroke). Additionally, macrophages from these plaques contained alternatively activated phenotypes, including subsets associated with plaque vulnerability. In plaques from asymptomatic patients, T cells and macrophages were activated and displayed evidence of interleukin-1β signaling. The identification of specific features of innate and adaptive immune cells in plaques that are associated with cerebrovascular events may enable the design of more precisely tailored cardiovascular immunotherapies.
2023-02-01 | GSE224273 | GEO
Project description:Genome wide Methylation profiling of DNA extracted from plaques of atherosclerotic plaque samples (n=14) and of controls (n=4). The Illumina Infinium HumanMethylation450 or HumanMethylation850 BeadChip was used representing potentially methylated CpG sites throughout the genome.
2021-08-31 | GSE149759 | GEO
Project description:Objective: Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. A cell-specific approach has the potential to address the question of gene expression differences between particular cell types in stable and unstable plaques with greater precision than approaches based on the study of whole plaques. Using laser micro-dissection, we isolated total RNA from macrophage-rich regions of stable and ruptured human atheromatous plaques derived from carotid endarterectomy samples which were comprehensively characterized using clinical, radiological and histological criteria, and carried out genome-wide gene expression profiling using microarrays. Results: The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences (p<0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine signaling pathway were the most significantly upregulated in ruptured compared to stable plaques (p=5.4x10-7). Two key components of the pathway, fatty-acid binding-protein 4 (FABP4) and leptin, showed nine-fold (p=0.0086) and five-fold (p=0.0012) greater expression respectively in macrophages from ruptured plaques. Conclusions: We found differences in gene expression signatures between macrophages isolated from stable and ruptured human atheromatous plaques. Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential. Methods: We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptured human atherosclerotic plaques. Plaques present in carotid endarterectomy specimens were designated as stable or ruptured using clinical, radiological and histopathological criteria. Macrophage-rich regions were excised from 5 ruptured and 6 stable plaques by laser micro-dissection. Total RNA were subjected to two cycles of linear amplification. Transcriptional profiling was performed using Affymetrix HG-U133 plus 2.0 GeneChip arrays.
2012-12-31 | E-GEOD-41571 | biostudies-arrayexpress
Project description:Atherosclerotic plaque rupture is the etiology of ischemic stroke and myocardial infarction. Ribosome-depleted total RNA was sequenced from carotid plaques obtained from patients undergoing carotid endarterectomy with high-grade stenosis and either 1) a carotid-related ischemic cerebrovascular event within the previous 5 days ('recently ruptured,' n=6) or 2) an absence of a cerebrovascular event ('asymptomatic,' n=5). Examination of the differentially expressed genes supported the importance of inflammation and inhibition of proliferation and migration coupled with an increase in apoptosis. Thus, the transcriptome of recently ruptured plaques is enriched with transcripts associated with inflammation and fibrous cap thinning and support further examination of the role of B lymphocytes and interferons in atherosclerotic plaque rupture.
2022-08-10 | GSE198600 | GEO