Molecular Atlas of PM 2.5 Chemical Constituents on Cardiac Conduction: A Multiomics Landscape in Older Adults

作者：Wanying Shi, Wenyan Yan, Mengmeng Wang, Fuchang Deng, Huimin Ren, Jiuxuan Gao, Shuyi Zhang, Juan Liu, Jianlong Fang, Jiaonan Wang, Shilu Tong, Song Tang, Xiaoming Shi · 发表于：Environmental Science & Technology · 年份：2025 · DOI：10.1021/acs.est.5c05682 · 被引用次数：4 · 研究领域：Air Quality and Health Impacts、Air Quality Monitoring and Forecasting、Climate Change and Health Impacts

Ambient fine particulate matter (PM 2.5 ) exposure is well-documented for cardiovascular risks, however, limited evidence regarding the underlying mechanisms on cardiac conduction in the elderly, especially regarding longitudinal impacts. We aimed to identify key toxic inorganic elemental constituents in PM 2.5 linked to cardiac electrophysiological abnormalities, DNA methylation-mediated pathways and the complex interplay with gene expression. The associations of PM 2.5 and its inorganic chemical constituents with electrocardiography (ECG) parameters were analyzed in 348 measurements of the healthy elderly by mixture exposure models. Epigenomic analyses and bidirectional mediation analyses were conducted to explore the effect patterns of epigenetic changes. Integrated analysis were performed to identify the potential biological pathways. Mixture exposure models identified S and Pb as major contributors to prolonged QRS duration and QTc interval. Bidirectional mediation analysis combined high-dimension mediating analysis revealed 43 cytosine-phosphoguanine sites (CpGs) significantly mediated the association between exposure to PM 2.5, Pb, and S and ECG parameters, with about 90% showing weaker reverse mediation. Cis-eQTM analysis showed that PM 2.5 and S elements associated DMPs modulated downstream gene expression, influencing ECG parameters. Specifically, four CpGs and their annotated gene expressions ( HMBOX1, C1orf109, ATAD3A, and RINL ) showed consistent effects on these...