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

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Non-Coding RNA Pub Date : 2023-08-01 DOI:10.3390/ncrna9040043
Hao Chen, Syed Masood, Ana G Rappold, David Diaz-Sanchez, James M Samet, Haiyan Tong
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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.

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受控臭氧暴露对循环 microRNAs 以及血管和凝血生物标志物的影响:中介分析
暴露于臭氧(O3)会对呼吸系统和心血管造成不良影响。循环微RNA(miRNA)的改变可能会通过细胞间通信导致miRNA对信使RNA的转录后调控,从而导致暴露于臭氧对血管的不良影响。在这项研究中,我们探讨了暴露于臭氧是否会诱导循环 miRNAs 发生变化,从而介导对下游血管和凝血生物标志物的影响。23 名健康男性连续两天暴露于过滤空气和 300 ppb 的臭氧中 2 小时。数据采用混合效应模型和中介分析进行统计分析。结果显示,多种循环 miRNA(如 miR-19a-3p、miR-34a-5p)的表达水平与暴露于 O3 显著相关。通路分析表明,这些 miRNA 可预测下游生物标志物(如 D-二聚体、C 反应蛋白、肿瘤坏死因子 α (TNFα))水平的变化。中介分析表明,miR-19a-3p 可能是暴露于 O3 诱导的血液 TNFα 水平变化的重要中介因子[0.08 (0.01, 0.15),p = 0.02]。总之,这项初步研究表明,健康男性成年人暴露于 O3 会导致循环 miRNAs 发生变化,其中一些可能介导暴露于 O3 对血管的影响。
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来源期刊
Non-Coding RNA
Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
6.70
自引率
4.70%
发文量
74
审稿时长
10 weeks
期刊介绍: Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.
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