Dataset Information

ABCA1 and ABCG1 DNA methylation in epicardial adipose tissue of patients with coronary artery disease.

ABSTRACT:

Background

Recent 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.

Methods

Paired 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.

Results

DNA 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.

Conclusion

CAD 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.

SUBMITTER: Miroshnikova VV

PROVIDER: S-EPMC8627066 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

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.