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.

Epicardial Adipose Tissue Ceramides Are Related to Lipoprotein Lipase Activity in Coronary Artery Disease: Unfolding a Missing Link

“…Besides, CAD with concomitant carotid artery disease or peripheral artery disease was accompanied by decreased ABCA1 gene expression in EAT, indicating that the process of reverse cholesterol transport may be also impaired in EAT of CAD patients. 47 Our study has some potential limitations. First, the number of patients was rather small, nevertheless, it must be taken into account the difficulty to obtain human EAT samples; besides, rigorous exclusion criteria were applied.…”

“…Besides, CAD with concomitant carotid artery disease or peripheral artery disease was accompanied by decreased ABCA1 gene expression in EAT, indicating that the process of reverse cholesterol transport may be also impaired in EAT of CAD patients. 47…”

Evaluation of the participation of ABCA1 transporter in epicardial and mediastinal adipose tissue from patients with coronary artery disease

“…This could be due to the atheromatous process in patients with CAD occurring in the coronary arteries, where the closest adipose tissue is the EAT. In addition, it has been reported that ABCA1 mRNA expression is influenced by risk factors such as smoking, age, diet and obesity ( 28 ).…”

Role of ABCA1 in Cardiovascular Disease

“…Both gene mutations in ABCA1 and DNA methylation modifications lead to this mRNA transcription deficiency. Previous reports have revealed a relationship between ABCA1 promoter region methylation and CHD risk [ 251 , 252 , 253 , 254 , 255 ]. Infante, et al [ 256 ] reported that ABCA1 , TCF7 , NFATC1 , PRKCZ , and PDGFA DNA are highly methylated in the CD4+ and CD8+ T cells of patients with acute coronary syndrome (ACS) using epigenome-wide analysis [ 256 ].…”