Li Tiezheng, Xu Lisha, Shen Peng, Qiu Jie, Wang Yixing, Hu Jingjing, Guan Peng, Lin Hongbo, Jiang Zhiqin, Chen Kun, Wang Jianbing
Department of Public Health, and Department of Endocrinology of the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children's Health, Hangzhou, China.
Department of Chronic Disease and Health Promotion, Yinzhou District Center for Disease Control and Prevention, Ningbo, China.
Environ Pollut. 2025 Mar 1;368:125750. doi: 10.1016/j.envpol.2025.125750. Epub 2025 Jan 25.
Epidemiological studies have reported that atmospheric particulate matter (PM) contributes to ischemic stroke (IS). Biological studies also indicated that the pathway where PM induces IS involves several pathological processes. Moreover, exposure to PM can alter the expression of specific microRNAs (miRNAs) and ultimately accelerate the onset of IS by regulating related pathways. However, evidence on the role of miRNAs between PM and IS still needs to be fully elucidated. We used the miRNA sequencing datasets from the GEO (Gene Expression Omnibus) to screen miRNAs associated with IS. A nested case-control study was performed, including all incident ischemic stroke cases during the follow-up period and controls matched by age, sex, and entry seasons. Land use regression (LUR) models were constructed to estimate the levels of PM and PM. The real-time quantitative PCR (RT-qPCR) assay was applied to detect the expression of candidate miRNAs in plasma samples collected at baseline to verify whether candidate miRNAs differentially expressed between cases and controls. Mediation analyses were applied to evaluate whether PM could induce IS by affecting the expression of miRNAs. We screened 23 miRNAs expressed differentially between cases and controls from the GEO database. A total of 605 incident ischemic stroke patients were finally included in the case group, and 605 healthy controls were matched. The RT-qPCR assay detected 15 differentially expressed miRNAs. Mediating effects of hsa-miR-107, hsa-miR-320b, hsa-miR-423-5p, hsa-miR-483-5p, and hsa-miR-935 were observed for the associations between PM and IS, indicating that PM could promote IS by altering the expression of those miRNAs. In this nested case-control study, PM might induce IS by affecting the expression of hsa-miR-107, hsa-miR-320b, hsa-miR-423-5p, hsa-miR-483-5p and hsa-miR-935.
流行病学研究报告称，大气颗粒物（PM）与缺血性中风（IS）有关。生物学研究也表明，PM诱发IS的途径涉及多个病理过程。此外，暴露于PM可改变特定微小RNA（miRNA）的表达，并最终通过调节相关途径加速IS的发病。然而，关于miRNA在PM与IS之间作用的证据仍需充分阐明。我们使用来自基因表达综合数据库（GEO）的miRNA测序数据集来筛选与IS相关的miRNA。进行了一项巢式病例对照研究，包括随访期间所有新发缺血性中风病例以及按年龄、性别和入组季节匹配的对照。构建土地利用回归（LUR）模型来估计PM和PM的水平。应用实时定量PCR（RT-qPCR）检测在基线时采集的血浆样本中候选miRNA的表达，以验证候选miRNA在病例和对照之间是否差异表达。应用中介分析来评估PM是否可通过影响miRNA的表达诱发IS。我们从GEO数据库中筛选出23种在病例和对照之间差异表达的miRNA。病例组最终纳入605例新发缺血性中风患者，并匹配605名健康对照。RT-qPCR检测到15种差异表达的miRNA。观察到hsa-miR-107、hsa-miR-320b、hsa-miR-423-5p、hsa-miR-483-5p和hsa-miR-935在PM与IS的关联中起中介作用，表明PM可通过改变这些miRNA的表达促进IS。在这项巢式病例对照研究中，PM可能通过影响hsa-miR-107、hsa-miR-320b、hsa-miR-423-5p、hsa-miR-483-5p和hsa-miR-935的表达诱发IS。
