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.
Objective. To assess the expression of the leptin gene (LEP) in the epicardial (EAT) and subcutaneous (SAT) adipose tissue in coronary artery disease (CAD) patients.Methods. 107 people were examined: 87 with CAD (57 men, 30 women), 20 without CAD (10 men, 10 women). Biopsy of EAT, SAT, coronary angiography, heart computed tomography, blood leptin levels were estimate, mRNA expression of the LEP gene evaluated by PCR.Results. In CAD patients with multivessel coronary artery lesion, the level of blood leptin is the highest. The expression of the LEP gene in EAT is higher in men than in women, in men with CAD higher than in non-coronary artery disease patients, and with a multivascular coronary lesion higher than in a 1–2 vascular lesion. Expression of the LEP gene in EAT in women with CAD is higher than with no CAD, and does not depend on the severity of coronary atherosclerosis. In SAT, LEP gene expression in men with CAD is higher than without CAD; women with CAD are lower than without CAD. Expression of the LEP gene in SAT is higher in men with a multivascular lesion than in 1–2 vascular lesion, and lower in women with a multivascular damage.Conclusions. The expression of the leptin gene in women is higher in SAT, and in men in EAT. Expression of the leptin gene in EAT with CAD is higher than without CAD. The expression of the leptin gene in SAT in men with CAD, especially with multivessel lesions, is higher than without coronary artery disease.
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