短期空气污染和温度暴露与规范老化研究（NAS）参与者细胞外 microRNA 谱的变化。
Short-term air pollution and temperature exposure and changes in the extracellular microRNA profile of Normative Aging Study (NAS) participants.
机构信息
Program in Public Health, Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA; Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA, USA.
Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA, USA; Biogen Inc, Cambridge, MA, USA.
出版信息
Environ Int. 2023 Jan;171:107735. doi: 10.1016/j.envint.2023.107735. Epub 2023 Jan 10.
BACKGROUND
While the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes.
METHODS
We examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015. Our exposures were defined as same-day, two-day, three-day, one-week, two-week, and three-week moving averages of PM, NO, O, and temperature which were derived from high-resolution spatio-temporal models. The ex-miRNA profiles of the subjects were obtained during follow-up visits. We analyzed the data using a longitudinal quantile regression model adjusted for individual covariates, batch effects, and time trends. We adjusted for multiple comparisons using a false discovery rate (FDR) correction. Ex-miRNAs that were significantly associated with exposures were further investigated using pathway analyses.
RESULTS
We found that all the examined exposures were associated with changes in ex-miRNA profiles in our study, particularly PM which was responsible for most of the statistically significant results. We found 110 statistically significant exposure-outcome relationships that revealed associations with the levels of 52 unique ex-miRNAs. Pathway analyses showed these ex-miRNAs have been linked to target mRNAs, genes, and biological mechanisms that could affect virtually every organ system, and as such may be linked to multiple clinical disease presentations such as cardiovascular disease, respiratory disease, and neurological disease.
CONCLUSIONS
Air pollution and temperature exposures were significantly associated with alterations in the ex-miRNA profiles of NAS subjects with possible biological consequences.
背景
尽管空气污染和温度对健康的影响已得到广泛研究，但分子层面的影响仍知之甚少。细胞外 microRNAs（ex-miRNAs）具有作为诊断或预后生物标志物的潜力，或者作为细胞间信号分子发挥作用，从而介导环境暴露对健康结果的影响。
方法
我们研究了 1999 年至 2015 年期间，参与规范衰老研究（NAS）的个体短期暴露于空气污染和环境温度与 ex-miRNA 谱之间的关系。我们的暴露定义为 PM、NO、O 和温度的当日、两日、三日、一周、两周和三周移动平均值，这些值是从高分辨率时空模型中得出的。在随访期间获取了研究对象的 ex-miRNA 谱。我们使用纵向分位数回归模型分析数据，该模型调整了个体协变量、批次效应和时间趋势。我们使用错误发现率（FDR）校正进行了多次比较调整。使用通路分析进一步研究与暴露显著相关的 ex-miRNAs。
结果
我们发现，我们研究中的所有检查暴露都与 ex-miRNA 谱的变化相关，尤其是 PM，它导致了大部分具有统计学意义的结果。我们发现 110 个具有统计学意义的暴露-结果关系，这些关系揭示了与 52 个独特 ex-miRNA 水平相关的关系。通路分析表明，这些 ex-miRNAs 与可能影响几乎所有器官系统的靶 mRNAs、基因和生物学机制相关联，因此可能与多种临床疾病表现（如心血管疾病、呼吸道疾病和神经疾病）相关联。
结论
空气污染和温度暴露与 NAS 个体 ex-miRNA 谱的改变显著相关，可能具有生物学后果。
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