Wan Jindong, Liu Sen, Luo Tao, Yang Yi, Wang Dan, Wang Xinquan, Zhou Peng, Hou Jixin, Wang Peijian
Endocr Connect. 2024 Dec 19;14(1). doi: 10.1530/EC-24-0402. Print 2025 Jan 1.
Primary aldosteronism (PA) is a prevalent cause of endocrine hypertension characterized by an excess of aldosterone that can induce proinflammatory, prooxidant and profibrotic effects on the heart. Emerging evidence indicates a heightened incidence of atrial fibrillation (AF) in patients with PA, suggesting a significant association between the two conditions. However, the underlying mechanisms remain unclear. The purpose of this study was to investigate the molecular networks associated with the development of both PA and AF.
Datasets were obtained from the Gene Expression Omnibus database. Hub genes were identified by enrichment and protein-protein interaction analysis. These hub genes were subsequently validated via two independent external datasets: GSE60042 (PA microarray dataset) and GSE41177 (AF microarray dataset). Following the identification of shared genes, quantitative real-time polymerase chain reaction (qPCR) was employed to verify the reliability of the dataset and to further confirm the presence of shared genes in clinical samples.
The results of the common gene analysis revealed that immune and inflammatory responses may be shared features in the pathophysiology of PA and AF. One hub gene, specifically tumor necrosis factor superfamily member 10 (TNFSF10), was identified through various analyses and subsequently validated via qPCR. Compared with that in healthy controls, the expression level of TNFSF10 was lower in PA patients with AF.
Our findings indicate that TNFSF10 may play a role in the pathophysiology of AF complications associated with PA conditions, suggesting that it could serve as a potential target for the diagnosis or treatment of PA patients complicated with AF.
原发性醛固酮增多症（PA）是内分泌性高血压的常见病因，其特征是醛固酮过量，可对心脏产生促炎、促氧化和促纤维化作用。新出现的证据表明，PA患者心房颤动（AF）的发病率升高，提示这两种疾病之间存在显著关联。然而，其潜在机制仍不清楚。本研究的目的是调查与PA和AF发生相关的分子网络。
从基因表达综合数据库获取数据集。通过富集分析和蛋白质-蛋白质相互作用分析确定枢纽基因。随后通过两个独立的外部数据集对这些枢纽基因进行验证：GSE60042（PA微阵列数据集）和GSE41177（AF微阵列数据集）。在确定共享基因后，采用定量实时聚合酶链反应（qPCR）来验证数据集的可靠性，并进一步确认临床样本中共享基因的存在。
共同基因分析结果显示，免疫和炎症反应可能是PA和AF病理生理学的共同特征。通过各种分析确定了一个枢纽基因，即肿瘤坏死因子超家族成员10（TNFSF10），随后通过qPCR进行了验证。与健康对照组相比，合并AF的PA患者中TNFSF10的表达水平较低。
我们的研究结果表明，TNFSF10可能在与PA相关的AF并发症的病理生理学中发挥作用，提示它可能作为诊断或治疗合并AF的PA患者的潜在靶点。
