The effects of controlled ozone exposure on circulating microRNAs and vascular and coagulation biomarkers: a mediation analysis
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 resulted from miRNAs’ post-transcriptional regulation of messenger RNAs. 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 to filtered air and 300 ppb O3 for 2 hours on successive days. Blood miRNA and protein biomarkers were quantified after each exposure session. A mixed-effects model and a mediation analysis were applied for the statistical analysis. Expression levels of multiple circulating miRNAs (e.g., miR-19a-3p, miR-34a-5p) were significantly associated with O3 exposure and were predicted to regulate downstream biomarkers [e.g., D-dimer, C-reactive protein, tumor necrosis factor α (TNFα)]. Mediation analysis showed that miR-19a-3p was a significant mediator of O3–exposure induced changes in blood TNFα levels [-0.08 (-0.15, -0.01), p = 0.02]. In conclusion, O3 exposure resulted in changes in specific circulating miRNAs, among which miR-19a-3p may mediate the vascular inflammation of O3 exposure in healthy male adults.