Characterization of plasma-derived exosomal miRNA changes following traffic-related air pollution exposure: A randomized, crossover trial based on small RNA sequencing. (September 2022)

• Record Type: Journal Article
• Authors: Du, Xihao; Zhang, Qingli; Jiang, Yixuan; Zhu, Xinlei; Zhang, Yang; Liu, Cong; Niu, Yue; Cai, Jing; Chen, Renjie; Kan, Haidong
• Is Part Of: Environment international. Volume 167(2022)
• Publication Date: 2022-09
• Subjects: Traffic-related air pollution -- Exosome -- Small RNA sequencing -- miRNA -- Randomized, crossover trial; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2022.107430
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Highlights: The randomized, crossover trial design had the advantage of strong causal inference. First study evaluated changes of genome-wide exosomal miRNA following TRAP exposure. Affected exosomal miRNA play important roles in various cardiopulmonary diseases. Our findings provided novel epigenetic insights of TRAP exposure. Abstract: Background: The underlying mechanisms for health effects of traffic-related air pollution (TRAP) are still unclear. Small RNA sequencing (RNA-seq) in exosomes represents as a powerful approach to elucidate biological pathways in response to environmental exposure. We therefore aimed to explore impact of TRAP exposure on exosomal miRNAs. Methods: We performed a randomized, crossover study among 35 healthy college students in Shanghai, China. Participants were randomly assigned to 4-hour exposure in a traffic-polluted Road and in a traffic-free Park, respectively, intermitted by a washout period (at least 2 weeks). RNA-seq was conducted to identify plasma-derived exosomal miRNAs and the differential miRNAs were explored using linear mixed-effect models. Pathway enrichment was conducted using ingenuity pathway analysis. Further, we validated several selected miRNAs by droplet digital PCR (ddPCR). Results: The average concentrations of air pollutants including ultrafine particles, black carbon, nitrogen dioxide, and carbon dioxide were 2–3 times higher in the Road compared to those in the Park. We identified 271 exosomal miRNAs (212 up-regulated and 59 down-regulated) that were significantly associated with TRAP. We found 5 miRNAs with 242 experimentally validated mRNA targets that were involved in cardiovascular pathway, cytokine signaling, and immune response. The ddPCR analysis suggested that miR-3612, miR-21-5p, and miR-195-5p were significantly changed following TRAP exposure. Conclusions: For the first time this trial characterized the genome-wide changes of exosomal miRNA associated with TRAP exposure. The molecular profiling of exosomal miRNAs and "novel" associations of some miRNAs were useful for understanding on biological mechanisms for the adverse effects of TRAP.