Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary atherosclerosis
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ABSTRACT:
PROVIDER: PRJEB39701 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4403940_1.fastq.gz | Fastqsanger.gz | |||
| ERR4403940_2.fastq.gz | Fastqsanger.gz | |||
| ERR4403941_1.fastq.gz | Fastqsanger.gz | |||
| ERR4403941_2.fastq.gz | Fastqsanger.gz | |||
| ERR4403942_1.fastq.gz | Fastqsanger.gz |
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Project description:Innate immune cells importantly contribute to the pathphysiology of atherosclerotic cardiovascular disease CVD. Previous studies show that isolated innate immune cells from patients with atherosclerotic CVD have an activated phenotype. To understand the origin of this immune cell activation, we performed bone marrow aspiration in 10 male patients with severe coronary artery disease (based on coronary CT angiography) and 10 control subjects in whom coronary atherosclerosis was excluded. After flow sorting of HSCs, MPPs, and GMPs, we performed RNAseq.
2020-11-08 | E-MTAB-9399 | biostudies-arrayexpress
Project description:Atherosclerosis is the major cause of cardiovascular disease (CVD). Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. In patients with atherosclerotic CVD, leukocytes have a hyperinflammatory phenotype. We hypothesize that immune cell reprogramming in these patients occurs at the level of myeloid progenitors. We included 13 patients with coronary artery disease due to severe atherosclerosis and 13 subjects without atherosclerosis in an exploratory study. Cytokine production capacity after ex vivo stimulation of peripheral blood mononuclear cells (MNCs) and bone marrow MNCs was higher in patients with atherosclerosis. In BM-MNCs this was associated with increased glycolysis and oxidative phosphorylation. The BM composition was skewed towards myelopoiesis and transcriptome analysis of HSC/GMP cell populations revealed enrichment of neutrophil- and monocyte-related pathways. These results show that in patients with atherosclerosis, activation of innate immune cells occurs at the level of myeloid progenitors, which adds exciting opportunities for novel treatment strategies.
| S-EPMC7665893 | biostudies-literature
Project description:This study aims at identifying gene expression patterns in the whole blood that could differentiate patients with severe coronary atherosclerosis from subjects without detectable coronary artery disease (CAD), and assess associations of gene expression patterns with plaque features at coronary CT angiography (CCTA). Patients undergoing CCTA for suspected CAD, with no cardiovascular history, were enrolled. Coronary stenosis was quantified and CCTA plaque features were assessed. The whole-blood transcriptome was analyzed by RNA-Sequencing. We detected highly significant differences in the circulating transcriptome between patients with high-degree coronary stenosis (> 70%) at CCTA and subjects with the absence of coronary plaques. Noteworthy, regression analysis revealed expression signatures associated with Leaman score, segment involved score, segment-stenosis score, and plaque volume with density <150 HU at CCTA. This pilot study shows that patients with significant coronary stenosis are characterized by whole blood transcriptome profiles that may discriminate them from patients without CAD. Furthermore, our results suggest that whole blood transcriptional profiles may predict plaque characteristics.
2022-06-29 | GSE202625 | GEO
Project description:Small extracellular vesicles (sEVs)-derived circular RNAs (circRNAs) could regulate gene expression in recipient cells, and dysregulation of sEVs-derived circRNAs has been implicated in several diseases. However, the expression and function of sEVs-derived circRNAs in coronary atherosclerosis (CAD) remain unknown. In this study, we investigated global changes in the expression patterns of circRNAs in sEVs from coronary atherosclerosis-related monocytes.
2021-10-20 | GSE166126 | GEO
Project description:Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Differences in transcriptional activity of these cells might reflect the individual's atherosclerotic burden. Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without signs of CAD on angiography. All patients were on statin and aspirin treatment. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, macrophages and CD34+ progenitor cells was subjected to genome-wide expression analysis. Only CD14+ monocytes demonstrated that a small number of genes involved in activation was overexpressed in control patients, which was verified by real-time polymerase-chain reaction. In this pilot study, cautious matching of patients with severe atherosclerotic CAD with control patients without angiographic signs of coronary atherosclerosis did not reveal differences in transcriptional activity in four out of five different mononuclear cell types. In resting monocytes from patients without overt CAD some inflammatory genes were overexpressed as compared to patients with severe CAD. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers. Keywords: disease-state analysis In total 153 arrays were analyzed with 6 technical replicates (147 biological samples). CD34+ stem cells, CD4+ T-cells, resting CD14+ monocytes, stimulated monocytes and macrophages were analyzed, all from patient with severe coronary atherosclerosis or controls that had no coronary atherosclerosis as determined angiographically, and which were carefully matched for age and gender.
2008-12-01 | E-GEOD-9820 | biostudies-arrayexpress
Project description:We examined feasibility of a unique approach towards gaining insight into heritable risk for early atherosclerosis: surveying gene expression by endothelial cells from living subjects. Subjects <50 years old (mean 37, range 22-49) without obstructive coronary artery disease underwent coronary reactivity testing that identified them as having normal (NL) or abnormal (ABNL) coronary endothelial function. Cultures of Blood Outgrowth Endothelial Cells (BOEC) from 6 NLs and 13 ABNLs passed rigorous quality control and were used for microarray assessment of gene expression. Of nine genes differentially expressed at FDR<0.1%, we here focus upon ABNLs having elevated expression of HMGB1 which we unexpectedly found to be linked to low LAMC1 expression. This was corroborated by three of our past studies and confirmed bio-functionally. Compared to NL BOEC, ABNL BOEC released 13±3 fold more HMGB1 in response to LPS; and they deposited one-tenth as much LAMC1 into collagen subendothelial matrix during culture. Clinical follow-up data are provided for 4 NLs (followed 13.4±0.1 yr) and for 12 ABNLs (followed 9.1±4.5 yr). The known pathogenic effects of high-HMGB1 and low-LAMC1 predict that the combination would biologically converge upon the focal adhesion complex, to the detriment of endothelial shear responsiveness. This gene expression pattern may comprise a heritable risk state that promotes early coronary atherosclerosis. If so, the testing could be applied even in childhood, enabling early intervention. This approach offers a way to bridge the information gap between genetics and clinical phenotype.
2020-06-01 | GSE132651 | GEO
Project description:Endothelial Gene Expression Associated With Early Coronary Atherosclerosis
| PRJNA548581 | ENA
Project description:Rationale: Epicardial adipose tissue (EAT) has been independently associated with non-calcified, high-risk coronary plaques in low-to intermediate risk subjects. Recently, a bidirectional communication was shown between EAT and diseased coronary arteries. In high-risk patients it is unknown whether quantitative measures of EAT can capture, and which molecular players are involved in this mutual interplay. Objective: In a high-risk population, we aimed to determine how the volume of EAT is linked to coronary artery disease (CAD) and to identify potential EAT-deregulated pathways in CAD patients specifically related to coronary artery calcification (CAC). Methods and Results: In a prospective cohort of 574 degenerative severe aortic stenosis patients referred to cardiac surgery, we quantified fat depots by computed tomography (CT) and performed a comparative quantitative proteomics of thoracic fat, including EAT, mediastinal (MAT) and subcutaneous (SAT) adipose tissues. We did not find an independent association of EAT volume with the severity, distribution and complexity of coronary stenosis in invasive coronary angiography. Although, EAT volume was correlated with high CAC, its cardiovascular risk factors-adjusted association was not significant. Taking as reference non-CAD matched-patients and compared to MAT and SAT, EAT proteomic signature of CAD was characterized by up-regulation of pro-calcifying annexins (Annexin A2, ANXA2), fatty acid binding transporters (FABP4) and inflammatory signaling proteins, and by down-regulation of fetuin-A and redox state regulatory enzymes. In EAT, ANXA2 regulation was positively correlated with CAC. EAT gene expression studies confirmed overexpression of ANXA2 and FABP4 in CAD, but no expression of FETUA was detected. Compared with non-CAD, fetuin-A circulating levels were higher in CAD, whereas no fetuin-A pericardial fluid differences were found. Conclusions: In this high-risk cohort, EAT presented an imbalance of pro-calcifying, pro-inflammatory and lipid transporters mediators. These local EAT-mediated regulatory mechanisms were not reflected by the CT volume of EAT alone.
2022-03-04 | PXD008852 | Pride
Project description:Growing evidence correlated changes in bioactive sphingolipids, particularly sphingosine-1-phosphate (S1P) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in the initiation and progression of atherosclerosis. Yet, how sphingolipid metabolism and signaling change and contribute to endothelial dysfunction and atherosclerosis remain poorly understood. By using a mouse model of coronary atherosclerosis, we demonstrated that hemodynamic stress induces an early metabolic rewiring of endothelial sphingolipid de novo biosynthesis favoring S1P signaling over ceramide as protective response. Furthermore, our data are paradigm shift from the current believe that ceramide accrual contributes to endothelial dysfunction. The de novo biosynthesis of sphingolipids is commenced by serine palmitoyltransferase (SPT), and is downregulated by NOGO-B, an ER membrane protein. We showed that Nogo-B is upregulated by hemodynamic stress in myocardial endothelial cells (EC) of ApoE-/- mice and is expressed in the endothelium lining coronary lesions in mice and human. We demonstrated that mice lacking Nogo-B specifically in EC (Nogo-A/BECKOApoE-/-) were resistant to coronary atherosclerosis development and progression, and mortality. Fibrous cap thickness was significantly increased in Nogo-A/BECKOApoE-/- mice and correlated with reduced necrotic core and macrophage infiltration. Mechanistically, the deletion of Nogo-B in EC sustained the rewiring of sphingolipid metabolism towards S1P, imparting an atheroprotective transcriptional signature that refrain coronary atherogenesis and its progression. These findings also set forth the foundation for sphingolipid-based therapeutics to reduce the treat this condition.
2024-02-12 | GSE254426 | GEO
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