Petersburg Nuclear Physics Institute Named By B.P. Konstantinov of National Research Center "Kurchatov Institute", Gatchina, Russian Federation.
Pavlov First Saint Petersburg State Medical University, St.-Petersburg, Russian Federation.
BMC Cardiovasc Disord. 2021 Nov 27;21(1):566. doi: 10.1186/s12872-021-02379-7.
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.
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.
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.
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.
最近的研究集中在心脏外膜脂肪组织（EAT）在冠状动脉疾病（CAD）发展中的潜在作用。ABCA1 和 ABCG1 转运蛋白调节细胞胆固醇含量和胆固醇逆向转运。我们旨在确定 EAT 和皮下脂肪组织（SAT）中 ABCA1 和 ABCG1 基因的 DNA 甲基化和 mRNA 水平是否与 CAD 相关。
从 82 名接受择期心脏手术的患者中采集 EAT 和 SAT 配对样本，这些患者因冠状动脉旁路移植术（CAD 组，N=66）或瓣膜手术（NCAD 组，N=16）而接受手术。通过实时聚合酶链反应分析 EAT 和 SAT 样本中的 ABCA1 和 ABCG1 mRNA 水平，通过 Western 印迹法评估 EAT 样本中的 ABCA1 蛋白水平。通过焦磷酸测序对来自 CAD 组的 24 个样本和来自 NCAD 组的 9 个样本进行 ABCA1 和 ABCG1 DNA 甲基化分析。
与 NCAD 相比，CAD 患者 EAT 样本中的 ABCA1 启动子和 ABCG1 cg27243685 和 cg06500161 CpG 位点的 DNA 甲基化水平更高（21.92%对 10.81%，p=0.003；71.51%对 68.42%，p=0.024；46.11%对 37.79%，p=0.016）。在 CAD 患者中，EAT 样本中的 ABCA1 和 ABCG1 DNA 甲基化水平高于 SAT 样本（p<0.05）。与 NCAD 组相比，CAD 患者中伴有颈动脉疾病或外周动脉疾病的患者 EAT 样本中的 ABCA1 mRNA 水平降低（p=0.024）。EAT 样本中的 ABCA1 蛋白水平在 CAD 患者中趋于低于 NCAD 组（p=0.053）。SAT 样本中 ABCG1 cg27243685 位点的 DNA 甲基化水平与血浆甘油三酯浓度（r=0.510，p=0.008）、体重指数（r=0.556，p=0.013）和腰臀比（r=0.504，p=0.012）呈正相关。
CAD 与 EAT 中 ABCA1 和 ABCG1 的 DNA 高甲基化有关。伴有颈动脉疾病或外周动脉疾病的 CAD 伴有 EAT 中 ABCA1 基因表达减少。SAT 中 ABCG1 cg27243685 位点的 DNA 甲基化水平与高甘油三酯血症和肥胖有关。
