Transcriptome-wide N6-methyladenosine methylation landscape of coronary artery disease

Epigenomics ◽  
2021 ◽  
Author(s):  
Keyong Deng ◽  
Xiaotong Ning ◽  
Xiaoxiao Ren ◽  
Bin Yang ◽  
Jianxin Li ◽  
...  

Aim: To reveal transcriptome-wide N6-methyladenosine (m6A) methylome of coronary artery disease (CAD). Materials & methods: The m6A levels of RNA from peripheral blood mononuclear cells measured by colorimetry were significantly decreased in CAD cases. Transcriptome-wide m6A methylome profiled by methylated RNA immunoprecipitation sequencing (MeRIP-seq) identified differentially methylated m6A sites within both mRNAs and lncRNAs between CAD and control group. Results: Bioinformatic analysis indicated that differentially methylated genes were involved in the pathogenesis of atherosclerosis. MeRIP-quantitative real-time PCR assay confirmed the reliability of MeRIP-seq data. Finally, the rat carotid artery balloon injury model was performed to confirm the role of m6A demethylase FTO in neointima formation. Conclusion: Our study provided a resource of differentially methylated m6A profile for uncovering m6A biological functions in the pathogenesis of CAD.

2020 ◽  
Vol 72 (4) ◽  
pp. 465-471
Author(s):  
Peyman Nowrouzi-Sohrabi ◽  
Atefeh Seghatoleslam ◽  
Peyman Izadpanah ◽  
Mehran Erfani ◽  
Hassan Ahmadvand ◽  
...  

The aim of this study was to investigate the expression of long non-coding RNA urothelial carcinoma-associated 1 (UCA1) and its role in TNF-? production as one of the main inflammatory cytokines, in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and healthy non-CAD (NCAD) individuals as the control group. Fifteen CAD and 15 NCAD individuals were enrolled in the study. UCA1 expression in PBMCs and the plasma concentrations of interleukin (IL)-6, IL-22 and tumor necrosis factor (TNF)-? were assessed by real-time PCR and flowcytometry, respectively. UCA1 expression was not significantly different between the CAD and NCAD groups, however, its level was higher in PBMCs of regular aspirin users of both study groups. Furthermore, aspirin users showed a significantly lower plasma level of TNF-? in comparison to non-aspirin users. In addition, UCA1 expression was negatively correlated with the level of TNF-? in the total sample of the examined population. It seems that the increased levels of UCA1 may be an underlying mechanism for downregulation of TNF-? in aspirin users.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Marlies P Noz ◽  
Siroon Bekkering ◽  
Laszlo Groh ◽  
Tim MJ Nielen ◽  
Evert JP Lamfers ◽  
...  

Atherosclerosis is the major cause of cardiovascular disease (CVD). Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. In patients with atherosclerotic CVD, leukocytes have a hyperinflammatory phenotype. We hypothesize that immune cell reprogramming in these patients occurs at the level of myeloid progenitors. We included 13 patients with coronary artery disease due to severe atherosclerosis and 13 subjects without atherosclerosis in an exploratory study. Cytokine production capacity after ex vivo stimulation of peripheral blood mononuclear cells (MNCs) and bone marrow MNCs was higher in patients with atherosclerosis. In BM-MNCs this was associated with increased glycolysis and oxidative phosphorylation. The BM composition was skewed towards myelopoiesis and transcriptome analysis of HSC/GMP cell populations revealed enrichment of neutrophil- and monocyte-related pathways. These results show that in patients with atherosclerosis, activation of innate immune cells occurs at the level of myeloid progenitors, which adds exciting opportunities for novel treatment strategies.


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


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