The role of miRNAs in the associations between particulate matter and ischemic stroke: a nested case-control study

Abstract

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_2.5 and PM₁₀. 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.