Single Cell RNA Seq Reveals a Distinct Immune Landscape in Vulnerable Coronary Plaques.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE184073 | GEO | 2022/02/20
REPOSITORIES: GEO
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Project description:Single Cell RNA Seq Reveals a Distinct Immune Landscape in Vulnerable Coronary Plaques.
| PRJNA763099 | ENA
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: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: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:Acute coronary syndrome (ACS) mostly arises from so-called vulnerable coronary plaques, particularly prone for rupture. Vulnerable plaques comprise a specific type of plaque, called the thin-cap fibroatheroma (TFCA). A TCFA is characterized by a large lipid-rich necrotic core, a thin fibrous cap, inflammation, neovascularization, intraplaque hemorrhage, microcalcifications or spotty calcifications, and positive remodeling. Vulnerable plaques are often not visible during coronary angiography. However, different plaque features can be visualized with the use of intracoronary imaging techniques, such as intravascular ultrasound (IVUS), potentially with the addition of near-infrared spectroscopy (NIRS), or optical coherence tomography (OCT). Non-invasive imaging techniques, such as computed tomography coronary angiography (CTCA), cardiovascular magnetic resonance (CMR) imaging, and nuclear imaging, can be used as an alternative for these invasive imaging techniques. These invasive and non-invasive imaging modalities can be implemented for screening to guide primary or secondary prevention therapies, leading to a more patient-tailored diagnostic and treatment strategy. Systemic pharmaceutical treatment with lipid-lowering or anti-inflammatory medication leads to plaque stabilization and reduction of cardiovascular events. Additionally, ongoing studies are investigating whether modification of vulnerable plaque features with local invasive treatment options leads to plaque stabilization and subsequent cardiovascular risk reduction.
| S-EPMC8911129 | biostudies-literature
Project description:Pericoronary adipose tissue (PCAT) features on Computed Tomography (CT) have been shown to reflect local inflammation and increased cardiovascular risk. Our goal was to determine whether PCAT radiomics extracted from coronary CT angiography (CCTA) images are associated with intravascular optical coherence tomography (IVOCT)-identified vulnerable-plaque characteristics (e.g., microchannels (MC) and thin-cap fibroatheroma (TCFA)). The CCTA and IVOCT images of 30 lesions from 25 patients were registered. The vessels with vulnerable plaques were identified from the registered IVOCT images. The PCAT-radiomics features were extracted from the CCTA images for the lesion region of interest (PCAT-LOI) and the entire vessel (PCAT-Vessel). We extracted 1356 radiomic features, including intensity (first-order), shape, and texture features. The features were reduced using standard approaches (e.g., high feature correlation). Using stratified three-fold cross-validation with 1000 repeats, we determined the ability of PCAT-radiomics features from CCTA to predict IVOCT vulnerable-plaque characteristics. In the identification of TCFA lesions, the PCAT-LOI and PCAT-Vessel radiomics models performed comparably (Area Under the Curve (AUC) ± standard deviation 0.78 ± 0.13, 0.77 ± 0.14). For the identification of MC lesions, the PCAT-Vessel radiomics model (0.89 ± 0.09) was moderately better associated than the PCAT-LOI model (0.83 ± 0.12). In addition, both the PCAT-LOI and the PCAT-Vessel radiomics model identified coronary vessels thought to be highly vulnerable to a similar standard (i.e., both TCFA and MC; 0.88 ± 0.10, 0.91 ± 0.09). The most favorable radiomic features tended to be those describing the texture and size of the PCAT. The application of PCAT radiomics can identify coronary vessels with TCFA or MC, consistent with IVOCT. Furthermore, the use of CCTA radiomics may improve risk stratification by noninvasively detecting vulnerable-plaque characteristics that are only visible with IVOCT.
| S-EPMC10045206 | biostudies-literature
Project description:Although unstable atherosclerosis in the carotid bifurcation is a significant etiology behind ischemic stroke, clinical imaging methods to distinguish stable from vulnerable lesions are lacking and selection of patients for stroke-preventive intervention still relies on surrogate variables with moderate predictive power, such as the degree of luminal narrowing. Here we combined clinical and diagnostic imaging information by comuted tomography to select patients with calcified plaques for large scale molecular analysis, in an effort to increase our understanding of the pathophysiology behind carotid plaque instability as related to patient- and plaque- phenotype.
2019-06-01 | GSE125771 | GEO
Project description:Single-cell immune landscape of human atherosclerotic plaques
| PRJNA930443 | ENA
Project description:In this study, single-cell sequencing of the BALF of CARDS patients yielded the following results: (1) IL1B+ neutrophils were significantly increased in the BALF of CARDS patients with exacerbated disease, which was associated with poor prognosis of CARDS patients, and this type of neutrophils underwent fatty acid metabolism reprogramming in comparison with other types of neutrophils, which may be related to their high-inflammatory response. (2) IL1B+ neutrophils promoted TNF secretion from hyperinflammatory type M1 macrophages through a caspase-dependent pathway, suggesting that neutrophil-macrophage interactions play an important role in the mechanism of CARDS development.
2024-05-15 | GSE240580 | GEO
Project description:Atrial fibrillation (AF) is strongly associated with strokes, heart failure, and increased mortality. Inflammation plays a role in the pathophysiology of AF; however, how inflammation in AF is sustained and induces fibrosis is unclear. Therefore, this study aimed to identify the characteristic monocyte–macrophage heterogeneity and the cell–cell interactions between immune and non-immune cells at a single cell level in the left atrial (LA) tissues of patients with AF who underwent LA appendectomies. Myeloid cells were divided into five macrophage clusters, TNF+, two IL1B+, TREM2+, LYVE1+ resident macrophages, three monocyte clusters, five dendritic cell clusters, neutrophils, and mast cells. The CellChat analysis revealed that IL1B+ macrophages send epidermal growth factor (EGF) signalling to fibroblasts and resident macrophages send IGF1 singalling to cardiomyocytes. When compared to openly published control samples, Amphiregulin (AREG) was the most upregulated gene in monocytes and monocyte-derived IL1B+ macrophages in the AF group. We also found that AREG levels in serum were higher in patients with AF than controls. EGF signalling from IL1B+ macrophages could be therapeutic targets for AF, and AREG could be a functional biomarker for AF.
2024-06-01 | GSE261170 | GEO