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

BACKGROUND: MicroRNAs (miRNAs) are 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 be partly mediated through effects of PM2:5 on miRNAs that regulate cytokine expression. [ABSTRACT FROM AUTHOR]