Dataset Information

Downregulation of Sirt1 is correlated to upregulation of p53 and increased apoptosis in epicardial adipose tissue of patients with coronary artery disease.

ABSTRACT: The higher expression level of p53 in epithelial adipose tissue (EAT) has previously been reported in atherosclerosis. Since we hypothesized that the expression of p53 is modulated by Sirt1, the aim of this study was to determine the expression levels of Sirt1 and p53 and to investigate their correlation to apoptosis in EAT of patients with coronary artery disease (CAD). Thirty-five patients with more than 50 % stenosis in at least one of the main coronary arteries were considered as CAD group while 29 patients with no clinical signs of atherosclerosis who underwent open-heart surgery for valve replacement were classified as control group. EAT biopsy samples were collected from all participants during surgery. Sirt1, p53, Bax, and Bcl-2 gene expression levels were determined in EAT by qRT-PCR and Western blotting was carried out to assess Sirt1 and p53 protein levels. Hematoxylin and eosin staining was used for histopathological analysis. mRNA and protein levels of Sirt1 in EAT were significantly lower in patients with CAD compared with control group, whereas CAD patients showed greater p53 gene and protein expressions. In addition, inverse correlations were observed between Sirt1 and p53 at both mRNA and protein levels. The Bax and ratio of Bax/Bcl-2 gene expressions were higher in CAD group, but no difference was observed in Bcl-2 expression. Histopathological analysis showed apoptotic bodies and infiltrated immune cells in EAT of CAD group. Our results suggest that the Sirt1-p53 axis may involve in atherosclerosis by promotion of apoptosis.

SUBMITTER: Khanahmadi M

PROVIDER: S-EPMC7689241 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Downregulation of Sirt1 is correlated to upregulation of p53 and increased apoptosis in epicardial adipose tissue of patients with coronary artery disease.

Khanahmadi Mahdieh M Manafi Babak B Tayebinia Heidar H Karimi Jamshid J Khodadadi Iraj I

EXCLI journal 20201002

The higher expression level of p53 in epithelial adipose tissue (EAT) has previously been reported in atherosclerosis. Since we hypothesized that the expression of p53 is modulated by Sirt1, the aim of this study was to determine the expression levels of Sirt1 and p53 and to investigate their correlation to apoptosis in EAT of patients with coronary artery disease (CAD). Thirty-five patients with more than 50 % stenosis in at least one of the main coronary arteries were considered as CAD group w ...[more]

PMID: 33250679

Similar Datasets

Project description:BackgroundEpicardial adipose tissue (EAT) is closely related to coronary artery disease (CAD). Hemodynamically significant CAD has a worse prognosis and is more likely to benefit from revascularization. However, the specific relationship between EAT and hemodynamically significant CAD remains unclear.MethodsA total of 164 inpatients received single-photon emission computerized tomography-myocardial perfusion imaging (SPECT/MPI) and coronary angiography (CAG) between March 2018 and October 2019 at the Third Affiliated Hospital of Soochow University were enrolled in the retrospective cross-sectional study. Data on body mass index (BMI), hypertension, hyperlipidemia, diabetes mellitus (DM), active smoking, and symptoms were gathered. Epicardial fat volume (EFV) and coronary artery calcium (CAC) were quantified by noncontrast computed tomography (CT). Hemodynamically significant CAD was defined by coronary stenosis severity ≥50% with reversible perfusion defects in the corresponding areas of SPECT/MPI.ResultsA total of 37.8% of patients had hemodynamically significant CAD. Age and BMI increased with tertiles of EFV (P for trend =0.009 and P<0.001). The ratios of hemodynamically significant CAD in EFV from low to high were 16.4%, 37.0%, and 60.0%, respectively (P for the trend <0.001). In univariate regression analysis, EFV was associated with hemodynamically significant CAD [odds ratio (OR) per 10 cm3 =1.36; 95% confidence interval (CI): 1.20-1.55; P<0.001]. After correcting for traditional risk factors and CAC, EFV was firmly linked to hemodynamically significant CAD (OR per 10 cm3 =1.53; 95% CI: 1.25-1.88; P<0.001). With an increasing trend in EFV for the tripartite groups, the likelihood of hemodynamically significant CAD increased significantly (P for trend <0.001). There was a saturation effect between EFV and hemodynamically significant CAD according to the generalized additive model (GAM). When EFV <134.43 cm3, EFV was linearly correlated with hemodynamically significant CAD (OR per 10 cm3 =2.06; 95% CI: 1.45-2.94; P<0.001). When EFV ≥134.43 cm3, the hemodynamically significant CAD risk was steeper and gradually reached saturation. Hypertension affected the relationship between EFV and hemodynamically significant CAD (P for the interaction =0.02) with an interaction effect.ConclusionsThere was a robust relationship between EFV and hemodynamically significant CAD. After adjustment for confounders, we found that the risk of hemodynamically significant CAD onset increased nonlinearly for EFV above 134.4 cm3. This refined understanding of the relationship is helpful for the accurate clinical prediction of hemodynamically significant CAD.

Project description:BackgroundRecent studies have focused on the potential role of epicardial adipose tissue (EAT) in the development of coronary artery disease (CAD). ABCA1 and ABCG1 transporters regulate cell cholesterol content and reverse cholesterol transport. We aimed to determine whether DNA methylation and mRNA levels of the ABCA1 and ABCG1 genes in EAT and subcutaneous adipose tissue (SAT) were associated with CAD.MethodsPaired EAT and SAT samples were collected from 82 patients undergoing elective cardiac surgery either for coronary artery bypass grafting (CAD group, N = 66) or valve surgery (NCAD group, N = 16). ABCA1 and ABCG1 mRNA levels in EAT and SAT samples were analyzed using real time polymerase chain reaction, ABCA1 protein levels in EAT samples were assessed by western blotting. ABCA1 and ABCG1 DNA methylation analysis was performed in 24 samples from the CAD group and 9 samples from the NCAD group via pyrosequencing.ResultsDNA methylation levels in the ABCA1 promoter and ABCG1 cg27243685 and cg06500161 CpG sites were higher in EAT samples from patients with CAD compared with NCAD (21.92% vs 10.81%, p = 0.003; 71.51% vs 68.42%, p = 0.024; 46.11% vs 37.79%, p = 0.016, respectively). In patients with CAD, ABCA1 and ABCG1 DNA methylation levels were higher in EAT than in SAT samples (p < 0.05). ABCA1 mRNA levels in EAT samples were reduced in the subgroup of patients with CAD and concomitant carotid artery disease or peripheral artery disease compared with the NCAD group (p = 0.024). ABCA1 protein levels in EAT samples tended to be lower in CAD patients than in the NCAD group (p = 0.053). DNA methylation levels at the ABCG1 cg27243685 site positively correlated with plasma triglyceride concentration (r = 0.510, p = 0.008), body mass index (r = 0.556, p = 0.013) and waist-to-hip ratio (r = 0.504, p = 0.012) in SAT samples.ConclusionCAD is associated with ABCA1 and ABCG1 DNA hypermethylation in EAT. CAD with concomitant carotid artery disease or peripheral artery disease is accompanied by decreased ABCA1 gene expression in EAT. DNA methylation levels at the ABCG1 cg27243685 locus in SAT are associated with hypertriglyceridemia and obesity.

Project description:The biological functions of epicardial adipose tissue (EAT) remain largely elusive. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). Objectives of this study were to identify genes that are up- or down-regulated among three adipose tissues (AT), namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases. Samples were collected from patients undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in all three AT depots of six men using the lllumina® HumanWG-6 v3.0 expression BeadChips. Twenty-two and 73 genes were up-regulated in EAT compared to mediastinal and subcutaneous AT, respectively. Ninety-four genes were down-regulated in EAT compared to subcutaneous adipose depot. However, none were significantly down-regulated in EAT compared to mediastinal fat. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (epicardial > mediastinal > subcutaneous). The results of ADORA1 and PTGDS were confirmed by qPCR in 25 biological replicates. Overall, the transcriptional profiles of EAT and MAT were similar compared to the subcutaneous compartment. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD. Samples of epicardial, mediastinal and subscutaneous adipose tissue were collected from the chest of 6 male patients undergoing coronary artery bypass grafting surgeries. The RNA was labeled and hybridized using a standard Illumina protocol (https://icom.illumina.com/Login?ReturnUrl=%2ficom%2fsoftware.ilmn%3fid%3d214&id=214). Three pairwise comparison among the three adipose tissue were made using significance analysis of microarrays.

Dataset Information

Downregulation of Sirt1 is correlated to upregulation of p53 and increased apoptosis in epicardial adipose tissue of patients with coronary artery disease.

Publications

Downregulation of Sirt1 is correlated to upregulation of p53 and increased apoptosis in epicardial adipose tissue of patients with coronary artery disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets