Transcriptional Profiling of CD133+ Cells in Coronary Artery Disease and Effects of Exercise on Gene Expression
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE18608 | GEO | 2010/12/17
SECONDARY ACCESSION(S): PRJNA121435
REPOSITORIES: GEO
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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. 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.
2010-12-17 | E-GEOD-18608 | biostudies-arrayexpress
Project description:Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. Methodology/Principal Findings In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. Conclusion/Significance Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. miRNA array analysis of isolated platelets from subjects with premature coronary artery disease compared to healthy control subjects.
2011-09-30 | E-GEOD-28858 | biostudies-arrayexpress
Project description:Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. Methodology/Principal Findings In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. Conclusion/Significance Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls.
2011-10-01 | GSE28858 | GEO
Project description:Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AS) are the heart diseases accounting for the highest proportion of cardiac surgeries. Routine biomarkers for an earl detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis and to evaluate their severity with imaging techniques before they become advanced to the point where intervention or surgery have limited therapeutic benefit. Urine is an attractive biofluid for biomarker assessment, provided the noninvasive nature of its collection. Therefore, we conducted a shotgun proteomics analysis of urine collected from 12 CAD and/or AS patients and 11 cardiovascular disease-free controls, aiming at identification of putative molecular candidates that could differentiate these diseases from healthy subjects
2022-12-18 | PXD036800 | Pride
Project description:The circRNA profiles of 24 CAD patients and 7 controls were performed by microarray. Six classifiers were used to evaluate potential circRNAs biomarkers. The expression levels of candidate circRNAs were further verified by qRT-PCR in large cohorts. Logistic regression analysis and receiver operating characteristic were conducted to assess the diagnostic value. A total of 624 circRNAs and 171 circRNAs were significantly upregulated and downregulated, respectively, in CAD patients relative to controls. A four-circRNA signature was identified using six different classifiers. Among these four circRNAs, hsa_circ_001879 and hsa_circ_004104 were found significantly upregulated in validation cohorts. We offered a transcriptome-wide overview of aberrantly expressed circRNAs in CAD patients, and Hsa_circ_001879 and hsa_circ_004104 were replicated and identified to be significantly upregulated in CAD patients. Our results suggested that hsa_circ_001879 and hsa_circ_004104 might serve as diagnostic biomarkers for CAD.
2021-06-07 | GSE115733 | GEO
Project description:Dysregulation of long non-coding RNAs (lncRNAs) has been proven to be involved in the pathogenesis of coronary artery disease (CAD). However, it remains to be extensively explored.Using microarray, we performed the transcriptome-wide lncRNA and mRNAs expression profile in peripheral blood mononuclear cells (PBMCs) of 93 CAD patients and 48 healthy controls. Gene Ontology (GO) and pathway analysis for differentially expressed mRNAs was used to investigate underlying biological associations of differentially expressed lncRNAs and create path-net to depict interactions of significant pathways. We identified 1,210 lncRNAs and 890 mRNAs differentially expressed from the expression profile and validated selected 7 lncRNAs. Two novel lncRNA biomarkers, ENST00000444488.1 and uc010yfd.1, together with CAD risk factors had the better predictive performance for discriminating CAD patients from healthy controls, and ENST00000444488.1 could diagnose acute myocardial infarction (AMI) patients from non-AMI patients.
2019-08-17 | GSE113079 | GEO
Project description:Global gene expression profile of whole blood in patients with coronary artery disease (CAD) showed significant upregulation of 343 genes and down regulation of 151 genes as compared to controls (p<0.05). There was predominant differential regulation of inflammatory and immune response genes as well as early growth response genes in our dataset. Of the ten candidate genes selected for validation by real time PCR in an independent cohort, CXCL1, EGR3, IL8, PTGS2 and CD69 genes were up regulated and IFNG and FASLG down regulated in cases relative to controls. We selected 13 patients with angiographically confirmed coronary artery disease (CAD) between ages 40 - 55 years and 11 population-based asymptomatic controls with normal ECG and matched for age, gendre and common risk factors such as diabetes and hypertension to that of the cases. Global gene expression profiling was performed on the Agilent microarray platform.
2012-11-09 | E-GEOD-42148 | biostudies-arrayexpress
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:Aims: Exosomes exist in almost all body fluid and contain diverse biological contents which may be reflective of disease state. Circular RNAs (CircRNAs) are stable in structure and have a long half-life in exosomes without degradation, thus making them reliable biomarkers. However, the potential of exosomal circRNAs as biomarkers of coronary artery disease (CAD) remains to be established. Here we aimed to investigate the expression levels and the potential use of exosomal circRNAs as diagnostic biomarkers of CAD. Main methods: CircRNAs expression levels in exosomes obtained from three plasma samples from CAD patients and three paired controls were analyzed using RNA sequencing. Exosomal circRNAs obtained in the profiling phase were then verified in two-center validation cohorts. Finally, the ability of exosomal circRNAs, adjusting for Framingham Heart Study (FHS) risk factors, was determined to discriminate between CAD patients and non-CAD controls. Key findings: 355 circRNAs were differentially expressed between these two groups: 164 were upregulated, and 191 were downregulated. Here we selected potential circRNAs (fold change > 4, P < 0.05) as candidate biomarkers for further validation. Our data showed that only hsa_circ_0005540 was significantly associated with CAD (P < 0.0001). After adjustment for risk factors, hsa_circ_0005540 showed a high discriminatory power for CAD in ROC analyses (AUC = 0.853; 95% confidence interval [CI] = 0.799 - 0.906, P < 0.001). Significance: Our results suggest that plasma exosomal hsa_circ_0005540 can be used as a promising diagnostic biomarker of CAD.
2020-07-20 | GSE152498 | GEO
Project description:Gene expression profile in circulating leukocytes identifies patients with coronary artery disease Peter Sinnaeve, Mark Donahue, Peter Grass, Jacky Vonderscher, David Seo, Pascal Goldschmidt, Christopher Granger Department of Medicine, Duke University, Durham, NC, USA, Novartis Institute for Biomedical Research, Cambridge, Boston, MA, USA Introduction Systemic and local inflammation plays a prominent pathogenetic role in atherosclerotic coronary artery disease (CAD), but the relationship of phenotypic changes in circulating leukocytes and extent of CAD remains unclear. We have investigated whether gene expression patterns in circulating leukocytes are associated with presence and extent of CAD. Methods Patients undergoing coronary angiography were selected according to their Duke CAD index (CADi), a validated angiographical measure of the extent of coronary atherosclerosis that correlates with outcome. RNA was extracted from 110 patients with CAD (CADi>23) and from 112 partially matched controls without CAD (CADi=0). Gene expression was assessed using Affymetrix U133A chips. Genes correlating with CAD were identified using Spearman’s rank correlation, and predictive gene expression patterns were identified using a partial least squares (PLS) regression analysis. Results 160 individual genes were found to significantly correlate with CADi (rho>0.2, P<0.0027), although changes in individual gene expression were relatively small (1.2 to 1.5 fold). Using these 160 genes, the PLS multivariate regression resulted in a highly predictive model (r2=0.764, P<0.001). Cross-validation showed that most of the predictive model was carried by only 8 genes (r2=0.752) (table 1). Conclusion Simultaneous expression pattern of 8 genes appears to be highly predictive for CAD. Peripheral leukocyte gene expression pattern could be a novel non-invasive biomarker for CAD and lead to new pathophysiologic insights. parallel group design
2008-10-31 | E-GEOD-12288 | biostudies-arrayexpress