scholarly journals Comprehensive analysis of the ceRNA network in coronary artery disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Weikang Bian ◽  
Xiao-Xin Jiang ◽  
Zhicheng Wang ◽  
Yan-Rong Zhu ◽  
Hongsong Zhang ◽  
...  

AbstractWith the rapid aging of the population, coronary artery disease (CAD) has become one of the most fatal chronic diseases. However, the genetic mechanism of CAD is still unclear. The purpose of this study is to construct the lncRNA-miRNA-mRNA regulatory network for CAD diseases and systematically identify differentially expressed genes in patients with coronary heart disease. In this study, two lncRNA datasets (GSE69587 and GSE113079) and a microRNA dataset (GSE105449) which contained 393 and 38 CAD samples were selected. In addition, two mRNA datasets which named GSE113079 (98 CAD samples) and GSE9820 (8 CAD samples) were selected to search the differentially expressed genes (DEGs). By comparing the expression data between CAD and control samples, a total of 1111 lncRNAs, 2595 mRNAs and 22 miRNAs were identified. Based on the DEGs, a lncRNA-miRNA-mRNA ceRNA network was constructed to explore the hub nodes in CAD. In the ceRNA network, the lncRNAs KCNQ1OT1 and H19 showed high connectivity with the nine miRNAs. GO and KEGG results showed that genes in ceRNA networks were mainly involved in nitrogen compound metabolic process, PI3K-Akt signaling pathway and retrograde endocannabinoid signaling. These findings will improve the understanding of the occurrence and development mechanism of CAD.

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 35 ◽  
Author(s):  
Meenashi Vanathi Balashanmugam ◽  
Thippeswamy Boreddy Shivanandappa ◽  
Sivagurunathan Nagarethinam ◽  
Basavaraj Vastrad ◽  
Chanabasayya Vastrad

Coronary artery disease (CAD) is a major cause of end-stage cardiac disease. Although profound efforts have been made to illuminate the pathogenesis, the molecular mechanisms of CAD remain to be analyzed. To identify the candidate genes in the advancement of CAD, microarray dataset GSE23766 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified, and pathway and gene ontology (GO) enrichment analyses were performed. The protein-protein interaction network was constructed and the module analysis was performed using the Biological General Repository for Interaction Datasets (BioGRID) and Cytoscape. Additionally, target genes-miRNA regulatory network and target genes-TF regulatory network were constructed and analyzed. There were 894 DEGs between male human CAD samples and female human CAD samples, including 456 up regulated genes and 438 down regulated genes. Pathway enrichment analyses revealed that DEGs (up and down regulated) were mostly enriched in the superpathway of steroid hormone biosynthesis, ABC transporters, oxidative ethanol degradation III and Complement and coagulation cascades. Similarly, geneontology enrichment analyses revealed that DEGs (up and down regulated) were mostly enriched in the forebrain neuron differentiation, filopodium membrane, platelet degranulation and blood microparticle. In the PPI network and modules (up and down regulated), MYC, NPM1, TRPC7, UBC, FN1, HEMK1, IFT74 and VHL were hub genes. In the target genes-miRNA regulatory network and target genes—TF regulatory network (up and down regulated), TAOK1, KHSRP, HSD17B11 and PAH were target genes. In conclusion, the pathway and GO ontology enriched by DEGs may reveal the molecular mechanism of CAD. Its hub and target genes, MYC, NPM1, TRPC7, UBC, FN1, HEMK1, IFT74, VHL, TAOK1, KHSRP, HSD17B11 and PAH were expected to be new targets for CAD. Our finding provided clues for exploring molecular mechanism and developing new prognostics, diagnostic and therapeutic strategies for CAD.


2014 ◽  
Vol 66 (3) ◽  
pp. 983-988 ◽  
Author(s):  
Hui Li ◽  
Xiaolan Zhong ◽  
Chaomin Li ◽  
Lijing Peng ◽  
Wei Liu ◽  
...  

Coronary artery disease (CAD) is the leading cause of death worldwide. Microarray analysis is a practical approach to study gene transcription changes that may reflect signatures that underlie the pathogenesis of CAD. Using gene expression profile data from the Gene Expression Omnibus database, we identified differentially expressed genes that can contribute to the pathology of CAD. Further pathway and network analyses were also implemented to identify pathways and hub genes related to the disease. We observed 466 downregulated and 560 upregulated genes. The ribosome pathway was the most significantly over-represented pathway with differentially expressed genes. Over 35% of the genes in this pathway were downregulated. Hub genes in the network, such as IL7R, FYN, CALM1 ESR1 and PLCG1, may play crucial roles in the pathogenesis of CAD. Our results facilitate the identification of molecular mechanisms that underlie CAD.


2021 ◽  
Author(s):  
Pei Du ◽  
Ren Guo ◽  
Keqin Gao ◽  
Shuang Yang ◽  
Baige Yao ◽  
...  

Background. Coronary artery disease (CAD) is a chronic inflammatory disease caused by development of atherosclerosis, which is the leading cause of mortality and disability. Our study aimed to identify the differentially expressed genes (DEGs) in CD14+ monocytes from CAD patients compared with those from non-CAD controls, which might pave the way to diagnosis and treatment for CAD. Methods. The RNA-seq was performed by BGISEQ-500, followed by analyzing with R package to screening differentially expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by R package. In addition, we validated the results of RNA-seq using RT-qPCR. Furthermore, we explored the function of selected ten genes in LDL-treated CD14+ monocytes by RT-qPCR. Results. a total of 2897 DEGs were identified, including 753 up- and 2144 down-regulated genes in CD14+ monocytes from CAD patients. These DEGs were mainly enriched in plasma membrane and cell periphery of cell component, immune system process of biological process, NF-kappa B signaling pathway, cell adhesion molecules signaling pathway and cytokine-cytokine receptor interaction signaling pathway. In LDL-treated CD14+ monocytes, the mRNA expression of PDK4 was significantly up-regulated. Conclusion. In this study, we suggested that PDK4 might play a role in progression of CAD. The study will provide some pieces of evidence to investigate the role and mechanism of key genes in the pathogenesis of CAD.


2009 ◽  
Vol 94 (1) ◽  
pp. 261-267 ◽  
Author(s):  
A. R. Baker ◽  
A. L. Harte ◽  
N. Howell ◽  
D. C. Pritlove ◽  
A. M. Ranasinghe ◽  
...  

Abstract Context: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated. Objectives: The objectives of the study were to: 1) examine key mediators of the nuclear factor-κB (NFκB) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects. Design: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies. Results: Western blotting showed epicardial AT had significantly higher NFκB, inhibitory-κB kinase (IKK)-γ, IKKβ, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-α. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 ± 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 ± 0.57 EU/ml; P<0.05]. Conclusion: Epicardial AT from patients with CAD shows increased NFκB, IKKβ, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFκB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Pradyumna Agasthi ◽  
Sivakanth Aloor ◽  
Avantika Chenna ◽  
Anekwe Onwuanyi

Background: Ghrelin (GH) is a gastrointestinal endocrine peptide regulating multiple biological processes including adipogenesis, glucose metabolism, cell differentiation and proliferation. Recent studies demonstrated that GH inhibits pro-atherogenic changes in vessel wall via inhibition of nuclear factor - B activity, a transcriptional factor mediating production pro-inflammatory cytokines and adhesion molecule expression in the endothelium. The aim of the current study is to conduct a meta-analysis to evaluate the relationship between serum GH levels and coronary artery disease (CAD). Methods: We searched MEDLINE, CINHAL and COCHRANE databases for studies reporting serum GH levels in the CAD and non CAD study population. We included case controls, cohort and cross-sectional studies. We calculated the weighted standardized mean difference (SMD) in serum GH levels between the CAD and control groups. Results: Our search strategy yielded 285 articles and we included 10 studies enrolling 1855 participants. The median age of the CAD group was 62 yrs. (IQR 60 - 63) compared to 61 yrs. (IQR 58 - 65) in the control group. The median body mass index in the CAD group was 28 kg/m2 (IQR 27.9 - 28) compared to 27 kg/m2 (IQR 26 - 27) in the control group. The unweighted median serum GH levels in the CAD group were 0.66 ng/ml (IQR 0.3 - 1.6) compared to 0.76 ng/ml (IQR 0.38 - 4.9) in the control group. The SMD of GH level was -0.44 (95% CI -0.56,-0.31) p<0.001 comparing those in the CAD group and control group. Conclusion: Serum GH levels are significantly and inversely associated with CAD. Current findings warrant the need to further investigate the role of GH in the pathogenesis of CAD.


2018 ◽  
Vol 17 (2) ◽  
pp. 290-295
Author(s):  
Premtim Rashiti ◽  
Ibrahim Behluli ◽  
Albiona Bytyçi

Objective: By enrolling a prospective study of 82 patients that underwent non-urgent coronary angiography for coronary artery disease (CAD), it is aimed to investigate the correlation between adiponectin and waist-hip-ratio with severity of CAD.Materials and methods: The results of the angiography, divided the patients into two groups, patients admitted with a diagnosis of CAD and non-CAD. In the conducted hospital based research, two groups were involved: the study group with documented angiographically CAD and control group without angiographic evidence of CAD. Some of the baseline adiponectin levels in stored serum samples of all patients, anthropometric and biochemical risk factors were assessed in both groups.Result and discussion: As the result, we have seen the presence of CAD that was associated with current smoking, male gender, waist–hip ratio (WHR).While, no significant difference between median adiponectin levels at baseline were observed between cases and controls.Conclusion: There is a significant positive correlation between waist - hip ratio and presence of severity of coronary artery disease.Bangladesh Journal of Medical Science Vol.17(2) 2018 p.290-295


PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0216363 ◽  
Author(s):  
Barbara Rizzacasa ◽  
Elena Morini ◽  
Ruggiero Mango ◽  
Chiara Vancheri ◽  
Simone Budassi ◽  
...  

2010 ◽  
Vol 119 (8) ◽  
pp. 335-343 ◽  
Author(s):  
Chiara Taurino ◽  
William H. Miller ◽  
Martin W. McBride ◽  
John D. McClure ◽  
Raya Khanin ◽  
...  

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=2.2×10−16). 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.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ji-Ren Peng ◽  
Ting-Ting Lu ◽  
Hao-Teng Chang ◽  
Xuan Ge ◽  
Bian Huang ◽  
...  

Aims. To measure plasma levels of superoxide dismutases 1, 2, and 3 (SOD1, 2, 3) and determine whether SODs can function as biomarkers for coronary artery disease (CAD).Patients & Methods. Patient groups were as follows: patients with stable angina pectoris (SAP,n=33), patients with acute coronary syndrome (ACS,n=49), and controls (n=42). Protein quantification was done using ELISA.Results. The concentrations of plasma SOD1 and SOD2 were higher in CAD than in healthy controls. No difference in SOD3 levels between CAD and control groups was found. Limited correlations were found between SODs and gender, age, and severity of coronary artery stenosis.Conclusions. Plasma levels of SOD1 and SOD2 were elevated in patients with CAD and might serve as surrogate biomarkers for CAD.


Author(s):  
Wen-Feng Ji ◽  
Jia-Xin Chen ◽  
Shu He ◽  
Ya-Qing Zhou ◽  
Lei Hua ◽  
...  

Objective: Circular RNAs (circRNAs) function as promising biomarkers and therapeutic targets for coronary artery disease due to their high stability, covalently closed structure and potential gene regulation. We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary artery disease (CAD). Methods: We performed RNA sequence analysis of circRNAs in peripheral blood mononuclear cells of 5 CAD patients and 5 controls. Bioinformatics analyses was adopted to explore biological functions of differentially expressed circRNAs. The miRanda and TargetScan tools were used to predict the miRNA targeting interactions and to construct a triple network of differentially expressed gene-circRNA-miRNA-mRNA. Results: In total, 13160 downregulated and 12905 upregulated circRNAs were identified in CAD. A gene ontology annotation analysis showed that genes in the network were involved in organelle organization, cell cycle, mitotic cycle and cellular metabolic process. Parental genes of the 10 dysregulated-circRNAs were involved in metabolism and protein modification, and these circRNAs might regulate gene expression associated with CAD via miRNA sponges. Conclusion: As potential ceRNAs, dysregulated circRNAs may be involved in the pathogenesis of CAD, which provides new insights into diagnosis and prognosis of coronary artery disease.


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