Circulating metals, leukocyte miRNAs and cardiovascular effects: Potential role of inflammatory and immune-related pathways

作者：Wending Li, Xuedan Xu, Qin Jiang, Pinpin Long, Yang Xiao, Yufei Wang, Yutong You, Chengyong Jia, Jie Qu, Wei Wang, Yanshou Lei, Jianjian Xu, Shuping Ruan, Xiaozheng Wang, Chaolong Wang, Huan Guo, Tangchun Wu, Yu Yuan · 发表于：Environmental Chemistry and Ecotoxicology · 年份：2025 · DOI：10.1016/j.enceco.2025.09.021 · 研究领域：MicroRNA in disease regulation、Biomarkers in Disease Mechanisms、Trace Elements in Health

Exposure to metals may elicit multiple cardiovascular effects, potentially through inflammation and immune dysregulation. Leukocyte functions are tightly regulated by microRNAs (miRNAs), but their roles in metal-induced cardiovascular effects remain largely unclear. In a panel of 160 Chinese adults, we aim to investigate the cross-sectional association of metal-associated leukocyte miRNAs with 10 cardiovascular indices (including blood pressure, heart rate variability [HRV], and arterial stiffness indices), and further explore whether inflammatory and immune-related pathways may mediate such associations. Of the 55 metal-associated leukocyte miRNAs, 3 miRNAs were significantly associated with blood pressure indices, 3 miRNAs with HRV indices, and 14 miRNAs with arterial stiffness (all P < 0.05). Of note, one nickel-associated miRNA, miR-27a-5p, showed positive associations with both blood pressure and arterial stiffness indices. We further identified 691 inflammatory and immune-related pathways potentially regulated by metal-associated miRNAs, with 7 pathways potentially mediating the associations between metal-associated miRNAs and cardiovascular indices. Notably, two pathways (B-1a B cell differentiation and activation of plasma proteins involved in acute inflammatory response) may mediate the positive associations of miR-27a-5p with blood pressure and with arterial stiffness, respectively. Our study, albeit exploratory, revealed novel associations between metal-associated ...