scholarly journals Integrated DNA methylation and gene expression analysis in the pathogenesis of coronary artery disease

Aging ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1486-1500 ◽  
Author(s):  
Liu Miao ◽  
Rui-Xing Yin ◽  
Qing-Hui Zhang ◽  
Xi-Jiang Hu ◽  
Feng Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coronary Artery Disease ◽  
Dna Methylation ◽  
Coronary Artery ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Artery Disease

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

2010 ◽  
Vol 119 (8) ◽  
pp. 335-343 ◽  
Author(s):  
Chiara Taurino ◽  
William H. Miller ◽  
Martin W. McBride ◽  
John D. McClure ◽  
Raya Khanin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Gene Expression Profiling ◽  
Whole Blood ◽  
Expression Profiling ◽  
Gene Expression Analysis ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Artery Disease

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.

scholarly journals Expression of adipocytokine genes and their content in various adipose tissue sites in patients with heart diseases

2020 ◽  
Author(s):  
Olga Gruzdeva ◽  
Yulia Dyleva ◽  
Ekaterina Belik ◽  
Daria Borodkina ◽  
Maxim Sinitsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coronary Artery Disease ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Mitral Valve ◽  
Valve Replacement ◽  
Mitral Valve Replacement ◽  
Biologically Active ◽  
Fat Depots ◽  
Artery Disease

Abstract Background Adipose tissue (AT) is an endocrine and paracrine organ that synthesizes biologically active adipocytokines, which affect inflammation, fibrosis, and atherogenesis. Epicardial and perivascular fat depots are of great interest owing to potential effects on the myocardium and blood vessels. Objective To assess expression and secretion of adipocytokine genes in adipose tissue in patients coronary artery disease (CAD) and patients with aortic or mitral valve replacement. Methods The study included 84 patients with CAD and 50 patients with aortic or mitral valve replacement. Adipocytes were isolated from subcutaneous (SAT), epicardial (EAT), and perivascular AT (PVAT) samples. Isolated adipocytes were cultured for 24 h after which, gene expression and secretion levels of selected adipokines and cytokines in the culture medium were determined. Results The study parameters differed depending on the adipose tissue location. EAT adipocytes in CAD patients were characterized by a pronounced imbalance in the adipokine system. EAT had the lowest adiponectin gene expression and secretion, regardless of nosology and high expression levels of the leptin gene, its receptor, and interleukin-6 (IL-6) were detected. High leptin and IL-6 levels resulted in increased pro-inflammatory activity, as observed in both EAT and PVAT adipocytes, especially in individuals with coronary artery disease. Conclusion The "protective" potential of adipose tissue depends on its location.

scholarly journals Genetic and epigenetic associations of ANRIL with coronary artery disease and risk factors

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Bayi Xu ◽  
Zhixia Xu ◽  
Yequn Chen ◽  
Nan Lu ◽  
Zhouwu Shu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Dna Methylation ◽  
Coronary Artery ◽  
Gene Dosage ◽  
Density Lipoprotein ◽  
Nucleotide Polymorphisms ◽  
Coronary Syndrome ◽  
Non Coding Rna ◽  
Artery Disease

Abstract Background Both DNA genotype and methylation of antisense non-coding RNA in the INK4 locus (ANRIL) have been robustly associated with coronary artery disease (CAD), but the interdependent mechanisms of genotype and methylation remain unclear. Methods Eighteen tag single nucleotide polymorphisms (SNPs) of ANRIL were genotyped in a matched case–control study (cases 503 and controls 503). DNA methylation of ANRIL and the INK4/ARF locus (p14ARF, p15INK4b and p16INK4a) was measured using pyrosequencing in the same set of samples (cases 100 and controls 100). Results Polymorphisms of ANRIL (rs1004638, rs1333048 and rs1333050) were significantly associated with CAD (p < 0.05). The incidence of CAD, multi-vessel disease, and modified Gensini scores demonstrated a strong, direct association with ANRIL gene dosage (p < 0.05). There was no significant association between ANRIL polymorphisms and myocardial infarction/acute coronary syndrome (MI/ACS) (p > 0.05). Methylation levels of ANRIL were similar between the two studied groups (p > 0.05), but were different in the rs1004638 genotype, with AA and AT genotype having a higher level of ANRIL methylation (pos4, p = 0.006; pos8, p = 0.019). Further Spearman analyses indicated that methylation levels of ANRIL were positively associated with systolic blood pressure (pos6, r = 0.248, p = 0.013), diastolic blood pressure (pos3, r = 0.213, p = 0.034; pos6, r = 0.220, p = 0.028), and triglyceride (pos4, r = 0.253, p = 0.013), and negatively associated with high-density lipoprotein cholesterol (pos2, r = − 0.243, p = 0.017). Additionally, we identified 12 transcription factor binding sites (TFBS) within the methylated ANRIL region, and functional annotation indicated these TFBS were associated with basal transcription. Methylation at the INK4/ARF locus was not associated with ANRIL genotype. Conclusions These results indicate that ANRIL genotype (tag SNPs rs1004638, rs1333048 and rs1333050) mainly affects coronary atherosclerosis, but not MI/ACS. There may be allele-related DNA methylation and allele-related binding of transcription factors within the ANRIL promoter.

scholarly journals DNA methylation of antisense noncoding RNA in the INK locus (ANRIL) is associated with coronary artery disease in a Chinese population

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chen-Hui Zhao ◽  
Hai-Tao Cao ◽  
Jing Zhang ◽  
Qiao-Wei Jia ◽  
Feng-Hui An ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Dna Methylation ◽  
Transcription Factor ◽  
Coronary Artery ◽  
Kegg Pathway ◽  
Cpg Island ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Pathway Enrichment Analysis ◽  
Artery Disease

Abstract To explore the association between methylation of antisense non-coding RNA in the INK4 locus (ANRIL) and coronary artery disease (CAD) development. Methylation levels of ANRIL in 100 subjects with CAD and 100 controls were quantitatively analyzed using Sequenom MassARRAY. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify novel pathways. Our analyses indicated that 7 to 8 CpG sites within the 2nd CpG island located upstream of ANRIL, also known as cyclin-dependent kinase inhibitor 2B – antisense 1 (CDKN2B-AS1), are hyper-methylated in CAD subjects compared to controls (p = 0.034). The 40th CpG site within the 2nd CpG island located upstream of CDKN2B-AS1 was methylated to a lesser extent in CAD subjects compared to controls (p = 0.045). Both Pearson and Spearman analyses indicated that methylation levels were significantly associated with total cholesterol (r = 0.204, p = 0.004), fasting high-density lipoprotein cholesterol (r = 0.165, p = 0.020), and fasting low-density lipoprotein cholesterol (r = 0.265, p = 0.000). KEGG pathway analysis revealed a significant enrichment of genes associated with the tumor necrosis factor (TNF) signaling pathway. Among them, CCAAT/enhancer binding protein (C/EBPβ) was identified as a key transcription factor that promotes expression of CDKN2B-AS1 through promotor interaction. DNA methylation of the ANRIL promoter was significantly associated with CAD development in our study. Our analyses suggest that C/EBPβ is a key transcription factor that promotes CDKN2B-AS1 expression by directly interacting with the gene promotor mediated by TNF signaling.

Identification of the molecular subgroups in coronary artery disease by gene expression profiles

2019 ◽  
Vol 234 (9) ◽  
pp. 16540-16548 ◽  
Author(s):  
Xiao‐Yan Peng ◽  
Yong Wang ◽  
Haibo Hu ◽  
Xian‐Jin Zhang ◽  
Qi Li
Keyword(s):  
Gene Expression ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Subgroups ◽  
Artery Disease
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