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

Chen, Hao; Masood, Syed; Rappold, Ana G.; Diaz-Sanchez, David; Samet, James M.; Tong, Haiyan

doi:10.3390/ncrna9040043

Open AccessArticle

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

by

Hao Chen

^1,†,‡

,

Syed Masood

^2,†,

Ana G. Rappold

³

,

David Diaz-Sanchez

³,

James M. Samet

³ and

Haiyan Tong

^3,*

¹

Oak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USA

²

Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

³

Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, 104 Mason Farm Rd, Chapel Hill, NC 27514, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

Current address: Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, 22 Shuangyong Rd, Nanning 530021, China.

Non-Coding RNA 2023, 9(4), 43; https://doi.org/10.3390/ncrna9040043

Submission received: 1 February 2023 / Revised: 6 July 2023 / Accepted: 28 July 2023 / Published: 1 August 2023

(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)

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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.

Keywords: microRNA; ozone; vascular biomarker; mediation; miR-19a-3p; TNFα

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MDPI and ACS Style

Chen, H.; Masood, S.; Rappold, A.G.; Diaz-Sanchez, D.; Samet, J.M.; Tong, H. Effects of Controlled Ozone Exposure on Circulating microRNAs and Vascular and Coagulation Biomarkers: A Mediation Analysis. Non-Coding RNA 2023, 9, 43. https://doi.org/10.3390/ncrna9040043

AMA Style

Chen H, Masood S, Rappold AG, Diaz-Sanchez D, Samet JM, Tong H. Effects of Controlled Ozone Exposure on Circulating microRNAs and Vascular and Coagulation Biomarkers: A Mediation Analysis. Non-Coding RNA. 2023; 9(4):43. https://doi.org/10.3390/ncrna9040043

Chicago/Turabian Style

Chen, Hao, Syed Masood, Ana G. Rappold, David Diaz-Sanchez, James M. Samet, and Haiyan Tong. 2023. "Effects of Controlled Ozone Exposure on Circulating microRNAs and Vascular and Coagulation Biomarkers: A Mediation Analysis" Non-Coding RNA 9, no. 4: 43. https://doi.org/10.3390/ncrna9040043

APA Style

Chen, H., Masood, S., Rappold, A. G., Diaz-Sanchez, D., Samet, J. M., & Tong, H. (2023). Effects of Controlled Ozone Exposure on Circulating microRNAs and Vascular and Coagulation Biomarkers: A Mediation Analysis. Non-Coding RNA, 9(4), 43. https://doi.org/10.3390/ncrna9040043

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

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