Fine Particulate Air Pollution and the Expression of microRNAs and Circulating Cytokines Relevant to Inflammation, Coagulation, and Vasoconstriction

BACKGROUND: MicroRNAs (miRNAs) arc a key factor in epigenetic regulation of gene expression, but miRNA responses to fine particulate matter (PM2.5) air pollution and their potential contribution to cardiovascular effects of PM2.5 are unknown, OBJECTIVE: We explored the potential influence of PM2.5 on the expression of selected cytokines relevant to systemic inflammation, coagulation, and vasoconstriction, and on miRNAs that may regulate their expression. METHODS: We designed a double-blind, randomized crossover study in which true and sham air purifiers were used to expose 55 healthy young adult students in Shanghai, China, to reduced or ambient levels of indoor PM2.5 during two-week periods, and we measured the expression (mRNA and protein) of 10 serum cytokines, and miRNAs that target them, after each intervention period. We used linear mixed-effect models to estimate associations of the intervention, and time-weighted personal PM2.5 exposures, with the cytokines, mRNA, and miRNAs; we also explored potential mediation by miRNAs. RESULTS: The findings were generally consistent for associations with the intervention and for associations with an interquartile range increase in time-weighted PM2.5. Specifically, higher PM2.5 exposure was positively associated with the expression (mRNA, protein, or both) of interleukin-1 (encoded by IL1, IL6, tumor necrosis factor (encoded by TNF), toll-like receptor 2 (encoded by TLR2), coagulation factor 3 (encoded by F3), and endothelin 1 (encoded by EDN1), and was negatively associated with miRNAs (miR-21-5p, miR-187-3p, miR-146a-5p, miR-1-3p, and miR-199a-5p) predicted to target mRNAs of IL1, TNF, TLR2, and EDN1. CONCLUSIONS: Our findings require confirmation but suggest that effects of PM2.5 on cardiovascular diseases may be related to acute effects on cytokine expression, which may he partly mediated through effects of PM2.5 on miRNAs that regulate cytokine expression.