RNA-seq of stable and unstable section of human atherosclerotic plaques
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE120521 | GEO | 2019/08/02
REPOSITORIES: GEO
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Project description:Transcriptional profiling of stable and unstable atherosclerotic plaque segments from human carotid endatrerectomies Objective Comparison of gene expression in stable versus unstable atherosclerotic plaque may be confounded by interpatient variability. The aim of this study was to identify differences in gene expression between stable and unstable segments of plaque obtained from the same patient. Human carotid endarterectomy specimens were segmented and macroscopically classified using a morphological classification system. Two analytical methods, an intraplaque and an interplaque analysis, revealed 170 and 1916 differentially expressed genes, respectively using Affymetrix gene chip analysis. A total of 115 genes were identified from both analyses. The differential expression of 27 genes was also confirmed using quantitative-polymerase chain reaction on a larger panel of samples. Eighteen of these genes have not been associated previously with plaque instability, including the metalloproteinase, ADAMDEC1 (37-fold), retinoic acid receptor responder-1 (5-fold), and cysteine protease legumain (3-fold). Matrix metalloproteinase-9 (MMP-9), cathepsin B, and a novel gene, legumain, a potential activator of MMPs and cathepsins, were also confirmed at the protein level. The differential expression of 18 genes not previously associated with plaque rupture has been confirmed in stable and unstable regions of the same atherosclerotic plaque. These genes may represent novel targets for the treatment of unstable plaque or useful diagnostic markers of plaque instability. Differential gene expression in stable and unstable plaque was assessed by whole transcriptome analysis. Intraplaque analysis by QT-PCR confirmed the differential expression of 18 genes not associated previously with plaque rupture. These genes may represent novel targets for the treatment of unstable plaque or useful diagnostic markers of plaque instability
2006-01-30 | E-TABM-190 | biostudies-arrayexpress
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: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: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.
2012-12-31 | GSE41571 | GEO
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
Project description:Plaque rupture and subsequent thrombus formation is responsible for the majority of clinical complications of atherosclerosis and nonetheless our understanding of what underlies plaque vulnerability and rupture is still sparse and mostly deductively based on animal models and in vitro studies. We adopted five different -omics platforms to compare ruptured atherosclerotic and advanced-stable tissue within the same carotid plaque specimen from 24 carotid endarterectomy patients. Segments designated as stable feature either a fibrous cap atheroma or pathological intimal thickening. Segments designated as ruptured include a thrombus and/or presented intraplaque hemorrhage. For the present study only those samples were selected for further analysis that were flanked by two segments of identical classification, be it stable (S) or ruptured (R); and were derived from CEA specimen that contained plaque segments of both classifications.
2014-05-17 | E-MTAB-2055 | 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: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:A biobank collection of carotid plaque samples taken from patients undergoing endarterectomy operations. Samples from carotid plaques and peripheral blood mononuclear cells in a setup with clinical registry data collection. See PMID 22371308 for further details.
2012-03-27 | E-GEOD-21545 | biostudies-arrayexpress
Project description:RNA-seq of stable and unstable section of human atherosclerotic plaques
| PRJNA493259 | ENA