Effects of ambient ozone exposure on circulating extracellular vehicle microRNA levels in coronary artery disease patients

ABSTRACT

Exposure to ambient air pollutants such as ozone (O₃) and particulate matter (PM) is associated with increased cardiovascular morbidity and rate of mortality, but the underlying biological mechanisms have yet to be described. Emerging evidence shows that extracellular vehicle (EV) microRNAs (miRNAs) may facilitate cell-to-cell and organ-to-organ communications and play a role in the air pollution-induced cardiovascular effects. This study aims to explore the association between air pollutant exposure and miRNA changes related to cardiovascular diseases. Using a panel study design, 14 participants with coronary artery diseases were enrolled in this study. Each participant had up to 10 clinical visits and their plasma samples were collected and measured for expression of miRNA-21 (miR-21), miR-126, miR-146, miR-150, and miR-155. Mixed effects models adjusted for temperature, humidity, and season were used to examine the association between miRNA levels and exposure to 8-hr O₃ or 24-hr PM_2.5 up to 4 days prior. Results demonstrated that miR-150 expression was positively associated with O₃ exposure at 1–4 days lag and 5day moving average while miR-155 expression tracked with O₃ exposure at lag 0. No significant association was found between miRNA expression and ambient PM_2.5 at any time point. β-blocker and diabetic medication usage significantly modified the correlation between O₃ exposure and miR-150 expression where the link was more prominent among non-users. In conclusion, evidence indicated an association between exposure to ambient O₃ and circulating levels of EV miR-150 and miR-155 was observed. These findings pointed to a future research direction involving miRNA-mediated mechanisms of O₃-induced cardiovascular effects.

KEYWORDS:

• Air pollutants
• PM_2.5
• ozone
• miRNA
• beta blocker
• repeated measures
• mixed effect model

Acknowledgments

The authors thank Dr. James Samet and Dr. Michael Breen for their review and suggestions.

Competing interests

The authors declare that they have no actual or competing interests.

Disclaimer

The research described in this article has been reviewed by the Center for Public Health and Environmental Assessment, U.S. EPA, and approved for publication. The contents of this article should not be construed to represent Agency policy nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Supplementary material

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Additional information

Funding

The U.S. Environmental Protection Agency Intramural Research Program supported this research.