Identifying candidate circulating RNA markers for coronary artery disease by deep RNA-Sequencing in human plasma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE208194 | GEO | 2022/11/02
REPOSITORIES: GEO
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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: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:This study aims to discover unknown LncRNAs associated with Coronary Artery Disease（CAD）in peripheral blood. Three pairs of clinical CAD group and control blood plasma samples were texted in this experiment by high-throughput sequencing methods. Cuffdiff software was used to get the expression profiles of LncRNAs, differentially expressed LncRNAs were identified based on fold change and p-value. Differently expressed genes in peripheral plasma and blood monocytes were verified by Q-PCR in large samples of clinical CAD group and controls. We find three LncRNAs uc003pxg.1, ENST00000565257, ENST00000568324 were up-regulated obviously in peripheral blood mononuclear cells of CAD patients and these outcomes were consistent with the sequencing results. The ideal LncRNAs were detected preliminarily. This founding lays the foundation for further research，and provides theoretical basis of LncRNA using for CAD early clinical screening.
2021-07-14 | GSE171551 | 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:Aim: To improve risk stratification in patients with stable coronary artery disease (CAD), we aimed to identify genes in monocytes predictive of new ischemic events in patients with CAD and determine to what extent expression of these transcripts resembles expression in acute myocardial infarction (AMI). Results: COX10 and ZNF484 distinguished between AMI and the whole group of stable CAD patients with an accuracy of 90%. COX10 and ZNF484 together with MT-COI and WNK1 distinguished AMI patients from stable CAD patients with and without a new event with a sensitivity of 89% and a specificity of 98%. MT-COI and COX10 increased the accuracy for separating stable CAD patients with and without a new coronary event from 68 to 80% in addition to age, gender, BMI, diabetes, lipids, blood pressure and hs-CRP. Interestingly, expression of MT-COI, COX10 and WNK1 (but not ZNF484) in PBMCs paired with that in monocytes; COX10 in whole blood was similar to that in monocytes. Conclusions: This work showed that COX10 and ZNF484, eventually combined with MT-COI and WNK1 have the potential to accurately discriminate between AMI and stable CAD patients, and may improve the risk assessment of stable CAD patients.
2019-08-13 | GSE129935 | 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:To understand the mechanism of coronary artery aneurysmal dilatation, we identified and compared the expression of circulating miRNAs in three groups of patients. Group 1 enrolled patients with aneurysmal dilatation of coronary arteries (n = 20), Group 2 included patients with angiographically confirmed coronary artery disease (CAD), whereas Group 3 included 20 patients with normal coronary arteries. The miRNAs were isolated from plasma and profiled using PCR arrays miRCURY LNA Serum/Plasma Focus PCR Panels. We demonstrated that the plasma miRNAs levels were significantly different in Group 1 in collation with Group 2 and Group 3 (fold change > 2 and p < 0.05). The comparison of Group 1 with Group 3 identified twenty-one significantly up-regulated and two down-regulated miRNAs in patients with aneurysmal coronary artery dilatation compared to the control groups. Moreover, we identified six up-regulated and two down-regulated miRNAs in patients with CAD compared to the controls. The third comparison revealed four up-regulated and three down-regulated miRNAs in Group 1, when compared to CAD patients. In conclusion, this study demonstrates the specific signature of plasma miRNA, namely up-regulated and down-regulated, in patients with abnormal dilatation of coronary arteries and the comparison between the groups consisting of atherosclerotic and control patients.
2022-03-18 | GSE198885 | GEO
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:This study describes a circulating miRNA signature of unstable angina (UA), which may be used as a novel biomarker for unstable coronary artery disease (CAD). The Taqman low-density miRNA array were used to identify distinct miRNA expression profiles in the plasma of patients with typical UA and angiographically documented CAD (UA group, n = 13) compared to individuals with non-cardiac chest pain (control group, n = 13). EDTA-plasma samples were obtained before the cardiac catheterization procedure.The study included 2 groups that were classified according to angiographic evidence and clinical evaluation of chest pain. Patients with chest pain or discomfort but with angiographic exclusion of coronary atherosclerosis were enrolled in the control group (n = 13). Chest discomfort referred to the following complaints: chest pain, pressure, tightness, or heaviness; pain that radiated to the neck, jaw, shoulders, back, or one or both arms; and persistent shortness of breath. Patients with typical unstable angina (UA) and angiographically documented CAD were enrolled in the UA group (n = 13).
2013-08-13 | E-GEOD-49823 | biostudies-arrayexpress
Project description:Apolipoprotein C-III was recently acknowledged as a prognostic marker for cardiovascular risk. High levels of Apo-CIII strongly correlate with hypertriglyceridemia and are associated with atherosclerosis and coronary heart disease (CAD). Aim of the present research was to study the plasma proteome profiles of stable CAD patients characterized by different levels of total Apo-CIII. Two subgroups of CAD patients with divergent concentrations (under and upper the median concentration of the population distribution=10mg/dL) of total circulating Apo C-III were examined using a shotgun proteomic approach. 180 plasma proteins of CAD patients were quantified and the data were analyzed by bioinformatic tools and multivariate statistics. The fold change analysis and the Partial Least Square Discriminant Analysis showed a clear separation of the two groups. The dynamic processes that involve Apo C-III concentration in blood and its relation with all other plasma proteins were considered. Lipoproteins (Apo C-II and Apo E), retinol-binding protein 4 and vitronectin were up-regulated in patients with high Apo C-III, while alpha 1-antitrypsin was down-regulated. In this pilot study, the different expression of plasma proteins through the entire range of concentrations of Apo C-III was defined, suggesting possible new players involved in the APO C-III-associated process of arterial damage
2018-07-05 | PXD005973 | Pride