1281 Mirnas in extracellular vesiclesmediate the effect of particulate matter exposure on coagulation in a large sample of overweight/obese adults

Introduction In Italy about 45% of people aged ≥18 years are overweight/obese and might thus be more susceptible to the adverse health effects of air pollution exposure. Particulate matter ≤10 µm (PM10) represents a common pollutant of living and working environments and has been associated with increased risk of cardiovascular diseases (CVD) and hypercoagulability. Extracellular vesicles (EV) might play an important role in PM-related CVD, as they can travel in body fluids and transfer miRNAs between cells. We investigated whether PM10 exposure is associated with changes in fibrinogen levels, EV release, and EV-miRNA content in a large sample of overweight/obese adults. Methods EV concentrations were quantified by nanoparticle tracking analysis and flow cytometry. To identify altered levels of EV-miRNAs, we profiled miRNAs of 883 subjects by the QuantStudio 12K Flex Real Time PCR System. The top 40 EV-miRNAs were validated through custom miRNA plates. Statistical analyses included multiple linear regressions, mediation analysis and bioinformatics analysis. Results In a sample of 1630 overweight/obese subjects from the SPHERE ( S usceptibility to P article H ealth E ffects, mi R NAs and E xosomes) study, short-term exposure to PM10 was associated with increased release of EVs, especially those from monocyte/macrophage components (CD14+) and platelets (CD61+). Nine EV-miRNAs (let-7c-5p; miR-106a-5p; miR-143–3 p; miR-185–5 p; miR-218–5 p; miR-331–3 p; miR-642–5 p; miR-652–3 p; miR-99b-5p) were downregulated in response to PM10 exposure and exhibited putative roles in CVD. Five of these nine EV-miRNAs were mediators in the positive association between PM10 exposure and fibrinogen levels. Conclusions Our study sheds some light on the potential mechanisms underlying the adverse cardiovascular health effects of air pollution exposure. Our results were obtained in a hypersusceptible population and thus strengthen the relevance of health promotion interventions for both the general public and the working population, as they might be particularly feasible in the workplace.