Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary atherosclerosis
Ontology highlight
ABSTRACT:
INSTRUMENT(S): NextSeq 500
ORGANISM(S): Homo sapiens
SUBMITTER: Bowen Zhang
PROVIDER: E-MTAB-9399 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Despite the significant reduction in the overall burden of cardiovascular disease (CVD) over the past decade, CVD still accounts for a third of all deaths in the United States and worldwide each year. While efforts to identify and reduce risk factors for atherosclerotic heart disease (i.e. hypertension, dyslipidemia, diabetes mellitus, cigarette smoking, inactivity) remain the focus of primary prevention, the inability to accurately and temporally predict acute myocardial infarction (AMI) impairs our ability to further improve patient outcomes. Our diagnostic evaluation for the presence of coronary artery disease relies on functional testing, which detects flow-limiting coronary stenosis, but we have known for decades that most lesions underlying AMI are only of mild to moderate luminal narrowings, not obstructing coronary blood flow. Accordingly, there is a dire need of improved diagnostics for underlying arterial plaque dynamics, fissure and rupture. Here we describe the designation of a specific gene expression pattern acting as a molecular signature for acute myocardial infarction present in whole blood of patients that was determined using microarray analysis of enriched circulating endothelial cells (CEC). We isolated circulating endothelial cells from patients experience acute myocardial infartion and healthy cohorts, and measured gene expression using the HG-133U_PLUS_2 microarray Circulating endothelial cells were isolated from patients experiencing acute myocardial infarction (n=49) and from healthy cohorts (n=50). The patients were separated into a discovery cohort (n=43) for biomarker discovery and model training; and into a validation cohort (n=56) for biomarker validation and model testing.
2015-02-28 | E-GEOD-66360 | biostudies-arrayexpress
Project description:Using the Illumina Infinium Human Methylation27 BeadChip, we performed a genome-wide analysis of DNA methylation in right coronary artery in the area of advanced atherosclerotic plaques, atherosclerotic-resistant internal mammary arteries, and great saphenous veins obtained from same patients with coronary heart disease. The resulting DNA methylation patterns were markedly different between all the vascular tissues. The genes hypomethylated in athero-prone arteries to compare with atherosclerotic-resistant arteries were predominately involved in regulation of inflammation and immune processes, as well as development. The great saphenous veins exhibited an increase of the DNA methylation age in comparison to the internal mammary arteries. Gene ontology analysis for genes harboring hypermethylated CpG-sites in veins revealed the enrichment for biological processes associated with the development. Four CpG-sites located within the MIR10B gene sequence and about 1 Kb upstream of the HOXD4 gene were also confirmed as hypomethylated in the independent dataset of right coronary arteries in the area of advanced atherosclerotic plaques in comparison with the other vascular tissues. Bisulfite converted genomic DNA from 24 samples was denatured, whole-genome amplified, fragmented and subsequently hybridized to the Illumina Infinium 27k Human Methylation Beadchip.
2014-10-31 | E-GEOD-62867 | biostudies-arrayexpress
Project description:Despite the significant reduction in the overall burden of cardiovascular disease (CVD) over the past decade, CVD still accounts for a third of all deaths in the United States and worldwide each year. While efforts to identify and reduce risk factors for atherosclerotic heart disease (i.e. hypertension, dyslipidemia, diabetes mellitus, cigarette smoking, inactivity) remain the focus of primary prevention, the inability to accurately and temporally predict acute myocardial infarction (AMI) impairs our ability to further improve patient outcomes. Our diagnostic evaluation for the presence of coronary artery disease relies on functional testing, which detects flow-limiting coronary stenosis, but we have known for decades that most lesions underlying AMI are only of mild to moderate luminal narrowings, not obstructing coronary blood flow. Accordingly, there is a dire need of improved diagnostics for underlying arterial plaque dynamics, fissure and rupture. Here we describe the designation of a specific gene expression pattern acting as a molecular signature for acute myocardial infarction present in whole blood of patients that was determined using microarray analysis of enriched circulating endothelial cells (CEC). We isolated circulating endothelial cells from patients experience acute myocardial infartion and healthy cohorts, and measured gene expression using the HG-133U_PLUS_2 microarray
2015-02-28 | GSE66360 | GEO
Project description:The rupture of atherosclerotic plaque contributes significantly to cardiovascular disease (CVD). Plasma concentrations of bilirubin, a by-product of heme catabolism, inversely associate with risk of CVD, although the link between bilirubin and atherosclerosis remains unclear.
2024-02-22 | PXD040314 | JPOST Repository
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:Inflammatory crosstalk between perivascular adipose tissue and and blood vessel wall may contribute to atherosclerosis pathogenesis, and exhibits more pro-inflammatory than adipogenic phenotype than subcutaneous adipocytes. To identify a genomic basis for biologic differences, we performed genome-wide expression to identiy expression genes differentially regulated between perivascular and subcutaneous adipocytes.for biologic differences. We performed global gene expression analyses on in vitro differentiated adipocytes from human left coronary artery perivascular adipose tissue and subcutaneous adipose tissues derived from unrelated donors who were non-obese and did not have any known metabolic or atherosclerotic disease.
2013-03-15 | E-GEOD-45169 | biostudies-arrayexpress
Project description:A comparison of global gene expression between rigorously defined stem and progenitor cells from patients with chronic myeloid leukaemia (CML) in chronic (CP), accelerated (AP) and blastic (BC) phase and similar populations isolated from normal volunteers. Cryopreserved CD34+ enriched cell populations obtained from patients with CML in CP, AP or BC at diagnosis prior to treatment -- or from normal volunteers -- were thawed and flow sorted into rigorously defined sub-populations (HSC, MPP, CMP, GMP and MEP -- using surface phenotype as described below). Total RNA was obtained and global gene expression measured following hybridisation to Affymetrix HuGene-1_0-st-v1 gene-chips. In total, 3 normal patient samples were compared with 6 CP, 4 AP and 2 BC samples. HSC, CMP, GMP and MEP populations were obtained from all specimens, MPP populations were obtained from normal, AP and BC specimens but not CP specimens.
2013-09-06 | E-GEOD-47927 | biostudies-arrayexpress
Project description:Cardiovascular disease (CVD) is the most common cause of death in patients with type II diabetes mellitus (T2DM). Although susceptibility to CVD is different for every patient, why some patients with T2DM develop CVD while others are protected has not yet been clarified. Patient-derived induced pluripotent stem cells (iPSCs) have been utilized to reveal the influence of genotype on phenotype and have the potential to connect a clinical phenotype to a causal gene. Using T2DM patient-derived iPSCs, we found that in patients protected from CVD there was significantly elevated expression of an esterase, arylacetamide deacetylase (AADAC) in vascular smooth muscle cells (VSMCs). To investigate the function of AADAC in CVD, we overexpressed this esterase in human primary coronary artery VSMCs and VSMCs differentiated from iPSCs and observed that the number of lipid droplets per cell was significantly diminished. Further metabolomic analyses revealed a marked reduction in storage lipids such as triacylglycerol and diacylglycerol and an increase in membrane phospholipids suggesting changes in the Kennedy pathway of lipid bioassembly. Cell migration, proliferation, and apoptosis were also significantly decreased in AADAC-overexpressing VSMCs. Moreover, apolipoprotein (Apo) E knockout mice overexpressing VSMC-specific Aadac showed significant amelioration of atherosclerotic lesions. Isolated VSMCs from these mice also displayed decreased lipid droplets, storage lipids, cell migration, proliferation, and apoptosis, all of which were consistent with human data. Our findings suggest that elevated AADAC expression in VSMCs protects T2DM patients from CVD. This study also highlights the potential of patient-derived iPSCs to investigate disease associated phenotypes as a means of elaborating the molecular mechanisms underlying disease pathology.
2020-05-18 | GSE113969 | GEO
Project description:LAD coronary atherosclerotic plaque gene expression
| PRJNA106929 | ENA
Project description:To investigate the expression profiles of miRNA in atherosclerotic plaques, the global features of miRNAs expression of three normal coronary artery tissues sample pools and three sample pools of advanced atherosclerosis plaques of coronary artery were studied using microarray technology,
2015-02-20 | E-MTAB-2460 | biostudies-arrayexpress