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Transcriptional Profiling of CD133+ Cells in Coronary Artery Disease and Effects of Exercise on Gene Expression

ABSTRACT: Bone marrow-derived progenitor cells are under investigation for cardiovascular repair, but may be altered by disease. We identified 82 differentially expressed genes in CD133+ cells from patients with coronary artery disease (CAD) versus controls, of which 59 were found to be up-regulated and 23 down-regulated. These genes were found to be involved in carbohydrate metabolism, cellular development and signaling, molecular transport and cell differentiation. Following completion of an exercise program, gene expression patterns resembled those of controls in 7 of 10 patients. Blood sampled from 4 healthy subjects (H), and from 10 patients with coronary artery disease at baseline (A) and after 3 months (B) of exercise.

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PROVIDER: S-DIXA-D-1048 | biostudies-other |

REPOSITORIES: biostudies-other

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Transcriptional profiling of CD133(+) cells in coronary artery disease and effects of exercise on gene expression.

Project description:BACKGROUND AIMS:Bone marrow (BM)-derived progenitor cells are under investigation for cardiovascular repair but may be altered by disease. Our aim was to identify differences in gene expression in CD133(+) cells of patients with coronary artery disease (CAD) and healthy controls, and determine whether exercise modifies gene expression. METHODS:CD133(+) cells were flow-sorted from 10 CAD patients and four controls, and total RNA was isolated for microarray-based gene expression profiling. Genes that were found to be differentially regulated in patients were analyzed further to investigate whether exercise had any normalizing effect on CD133(+) cells in CAD patients following 3 months of an exercise program. RESULTS:Improvement in effort tolerance and increases in the number of CD133(+) cells were observed in CAD patients after 3 months of exercise. Gene expression analysis of the CD133(+) cells identified 82 differentially expressed genes (2-fold cut-off, 25% false-discovery rate and % present calls) in patients compared with controls, of which 59 were found to be up-regulated and 23 down-regulated. These genes were found to be involved in carbohydrate metabolism, cell cycle, cellular development and signaling, and molecular transport. Following completion of the exercise program, gene expression patterns resembled those of controls in seven of 10 patients. CONCLUSIONS:Alterations in gene expression of BM-derived CD133(+) progenitor cells were found in CAD patients, which in part may be normalized by exercise.

| S-EPMC3052778 | biostudies-literature

Transcriptional Profiling of CD133+ Cells in Coronary Artery Disease and Effects of Exercise on Gene Expression

Project description:Bone marrow-derived progenitor cells are under investigation for cardiovascular repair, but may be altered by disease. We identified 82 differentially expressed genes in CD133+ cells from patients with coronary artery disease (CAD) versus controls, of which 59 were found to be up-regulated and 23 down-regulated. These genes were found to be involved in carbohydrate metabolism, cellular development and signaling, molecular transport and cell differentiation. Following completion of an exercise program, gene expression patterns resembled those of controls in 7 of 10 patients.

2010-12-17 | GSE18608 | GEO

Transcriptional Profiling of CD133+ Cells in Coronary Artery Disease and Effects of Exercise on Gene Expression

2010-12-17 | E-GEOD-18608 | biostudies-arrayexpress

Gene expression profiling in whole blood of patients with coronary artery disease.

Project description:Owing to the dynamic nature of the transcriptome, gene expression profiling is a promising tool for discovery of disease-related genes and biological pathways. In the present study, we examined gene expression in whole blood of 12 patients with CAD (coronary artery disease) and 12 healthy control subjects. Furthermore, ten patients with CAD underwent whole-blood gene expression analysis before and after the completion of a cardiac rehabilitation programme following surgical coronary revascularization. mRNA and miRNA (microRNA) were isolated for expression profiling. Gene expression analysis identified 365 differentially expressed genes in patients with CAD compared with healthy controls (175 up- and 190 down-regulated in CAD), and 645 in CAD rehabilitation patients (196 up- and 449 down-regulated post-rehabilitation). Biological pathway analysis identified a number of canonical pathways, including oxidative phosphorylation and mitochondrial function, as being significantly and consistently modulated across the groups. Analysis of miRNA expression revealed a number of differentially expressed miRNAs, including hsa-miR-140-3p (control compared with CAD, P=0.017), hsa-miR-182 (control compared with CAD, P=0.093), hsa-miR-92a and hsa-miR-92b (post- compared with pre-exercise, P<0.01). Global analysis of predicted miRNA targets found significantly reduced expression of genes with target regions compared with those without: hsa-miR-140-3p (P=0.002), hsa-miR-182 (P=0.001), hsa-miR-92a and hsa-miR-92b (P=2.2x10-16). In conclusion, using whole blood as a 'surrogate tissue' in patients with CAD, we have identified differentially expressed miRNAs, differentially regulated genes and modulated pathways which warrant further investigation in the setting of cardiovascular function. This approach may represent a novel non-invasive strategy to unravel potentially modifiable pathways and possible therapeutic targets in cardiovascular disease.

| S-EPMC2922838 | biostudies-literature

Effects of gradual coronary artery occlusion and exercise training on gene expression in swine heart.

Project description:Gradual occlusion (O) of the swine left circumflex coronary artery (LCX) with an ameroid occluder results in complete O within 3 weeks, collateral vessel development, and compensatory hypertrophy. The purpose of this investigation was to determine the independent and combined effects of O and exercise training (E) on gene expression in the swine heart. Adult Yucatan miniature swine were assigned to one of the following groups (n=6-9/group): sedentary control (S), exercise-trained (E), sedentary swine subjected to LCX occlusion (SO), and exercise-trained swine with LCX occlusion (EO). Exercise consisted of progressive treadmill running conducted 5 d/wk for 16 weeks. Gene expression was studied in myocardium isolated from the collateral-dependent left ventricle free wall (LV) and the collateral-independent septum (SEP) by RNA blotting. E and O each stimulated cardiac hypertrophy independently (p<0.001) with no interaction. O but not E increased atrial natriuretic factor expression in the LV, but not in the SEP. E decreased the expression of beta-myosin heavy chain in the LV, but not in the SEP. E retarded the expression of collagen III mRNA in SEP; but not in the LV. Exercise training and coronary artery occlusion each stimulate cardiac hypertrophy independently and induce different patterns of gene expression.

| S-EPMC2662753 | biostudies-literature

PHACTR1, a coronary artery disease risk gene, drives endothelial dysfunction

Project description:Recent genome-wide association studies have identified PHACTR1 as a critical risk gene associated with polyvascular diseases. However, it remains elusive how PHACTR1 is involved in endothelial dysfunction. Here, we show that PHACTR1 triggers endothelial inflammation by activating NF-κB and disrupts Nitric oxide production by inhibiting Akt/eNOS activation to induce endothelial diastolic disorder. Whereas, Atorvastatin particularly plays an inhibitory effect on PHACTR1 gene expression in a dose-dependent manner among PHACTR family in endothelial cells. PHACTR1 may interact with PP1 with coupling with heat shock protein 8 (HSPA8) to dephosphorylate Akt or eNOS.

2022-08-16 | PXD034213 | Pride

Diagnosis of Coronary Heart Diseases Using Gene Expression Profiling; Stable Coronary Artery Disease, Cardiac Ischemia with and without Myocardial Necrosis.

Project description:Cardiovascular disease (including coronary artery disease and myocardial infarction) is one of the leading causes of death in Europe, and is influenced by both environmental and genetic factors. With the recent advances in genomic tools and technologies there is potential to predict and diagnose heart disease using molecular data from analysis of blood cells. We analyzed gene expression data from blood samples taken from normal people (n = 21), non-significant coronary artery disease (n = 93), patients with unstable angina (n = 16), stable coronary artery disease (n = 14) and myocardial infarction (MI; n = 207). We used a feature selection approach to identify a set of gene expression variables which successfully differentiate different cardiovascular diseases. The initial features were discovered by fitting a linear model for each probe set across all arrays of normal individuals and patients with myocardial infarction. Three different feature optimisation algorithms were devised which identified two discriminating sets of genes, one using MI and normal controls (total genes = 6) and another one using MI and unstable angina patients (total genes = 7). In all our classification approaches we used a non-parametric k-nearest neighbour (KNN) classification method (k = 3). The results proved the diagnostic robustness of the final feature sets in discriminating patients with myocardial infarction from healthy controls. Interestingly it also showed efficacy in discriminating myocardial infarction patients from patients with clinical symptoms of cardiac ischemia but no myocardial necrosis or stable coronary artery disease, despite the influence of batch effects and different microarray gene chips and platforms.

| S-EPMC4773227 | biostudies-literature

LncRNA expression profiling for 6 human monocytes samples from Coronary Artery Disease patients and non Coronary Artery Disease patients

Project description:The human LncRNA microarray analysis of the 6 monocytes samples from Coronary Artery Disease patients and non Coronary Artery Disease

2015-06-05 | GSE69587 | GEO

LncRNA expression profiling for 6 human plasma samples from Coronary Artery Disease patients and non Coronary Artery Disease patients

Project description:The human LncRNA microarray analysis of the 6 plasma samples from Coronary Artery Disease patients and non Coronary Artery Disease

2015-05-05 | GSE68506 | GEO

Peripheral-blood gene expression profiling studies for coronary artery disease and its severity in Xinjiang population in China.

Project description:BackgroundAlterations in gene expression in peripheral blood cells play a curtail role in the presence and extent of coronary artery disease (CAD), but its severity reflected by gene expression alterations in peripheral blood cells is still unknown in Xinjiang population in China.MethodsGlobal gene expression profiling in peripheral blood was used to explore differentially expressed genes in coronary artery stenosis patients. RNA was extracted from peripheral blood of 9 controls without coronary stenosis and 21 cases with angiographically CAD. The extent of CAD severity was categorized angiographically as no CAD, mild CAD (20 to 50% luminal diameter stenosis [LDS]), moderate CAD (50 to 75% LDS) and severe CAD (≥75% LDS). Differentially expressed genes related with CAD severity from peripheral blood cells were screened by linear mixed effects analysis using the lme4 package in R. Then the differentially expressed genes that gradually up-regulated or down-regulated were enriched by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.ResultsThe most significantly enrichments were toll-like receptor signaling pathway, immune responses, translational processes, cellular growth, inflammation and metabolic processes. Combined with NCBI-GeneRIF and PubMed analysis, we focused on the 12 genes associated with toll-like receptor signaling pathway in the extent of coronary artery stenosis patients. Receiver operating characteristic (ROC) analysis of 12 genes associated with toll-receptor signaling pathway in the 236 CAD patients from GEO database demonstrated that 12 genes expression could predict severe CAD with an area under the curve of 0.67, sensitivity of 77.65% and specificity of 51.52%.ConclusionThese results suggest that 12 genes associated with toll-like receptor signaling pathway in peripheral-blood cells reflect the presence and extent of CAD severity in Xinjiang population in China.

| S-EPMC6052538 | biostudies-literature

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