Effects of Controlled Ozone Exposure on Circulating microRNAs and Vascular and Coagulation Biomarkers: A Mediation Analysis.

Abstract

Exposure to ozone (O₃) is associated with adverse respiratory and cardiovascular outcomes. Alterations in circulating microRNAs (miRNAs) may contribute to the adverse vascular effects of O₃ exposure through inter-cellular communication resulting in post-transcriptional regulation of messenger RNAs by miRNAs. In this study, we investigated whether O₃ exposure induces alterations in circulating miRNAs that can mediate effects on downstream vascular and coagulation biomarkers. Twenty-three healthy male adults were exposed on successive days to filtered air and 300 ppb O₃ for 2 h. Circulating miRNA and protein biomarkers were quantified after each exposure session. The data were subjected to mixed-effects model and mediation analyses for the statistical analyses. The results showed that the expression level of multiple circulating miRNAs (e.g., miR-19a-3p, miR-34a-5p) was significantly associated with O₃ exposure. Pathway analysis showed that these miRNAs were predictive of changing levels of downstream biomarkers [e.g., D-dimer, C-reactive protein, tumor necrosis factor α (TNFα)]. Mediation analysis showed that miR-19a-3p may be a significant mediator of O₃-exposure-induced changes in blood TNFα levels [0.08 (0.01, 0.15), p = 0.02]. In conclusion, this preliminary study showed that O₃ exposure of healthy male adults resulted in changes in circulating miRNAs, some of which may mediate vascular effects of O₃ exposure.