Perturbations of the arginine metabolome following exposures to traffic-related air pollution in a panel of commuters with and without asthma
Perturbations of the arginine metabolome following exposures to traffic-related air pollution in a panel of commuters with and without asthma
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DOI：
10.1016/j.envint.2019.04.003
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发表时间：
2019-06-01
影响因子：
11.8
通讯作者：
Sarnat, Jeremy A.
中科院分区：
文献类型：
--
作者：
Liang, Donghai;Ladva, Chandresh N.;Sarnat, Jeremy A.
背景资料：尽管有大量的观察性和对照研究报告了交通源与哮喘急性发作和住院之间的关系，但交通相关空气污染对哮喘患者影响的潜在机制仍不清楚。目的：为了确定交通污染暴露后受到干扰的分子途径，我们分析了亚特兰大通勤者暴露（ACE-2）研究的数据，方法：我们测量了27种空气污染物，并对45名通勤者每次暴露前后的血液样本进行了高分辨率代谢组学分析。我们评估代谢产物和代谢途径的干扰使用非靶向代谢组的关联研究框架与途径分析和化学annotation.Results：大多数测量的污染物在公路通勤升高（p < 0.05）。从负离子和正离子两种模式中，分别从血浆中提取了17，586和9087个代谢特征。在控制混杂因素和错误发现率后，494和220个独特特征分别与27次暴露中的至少3次相关（p < 0.05）。途径分析表明，多种炎症和氧化应激相关代谢途径发生了改变，包括白细胞三烯、维生素E、细胞色素P450和色氨酸代谢。我们鉴定并注释了45种在这些途径中富集的独特代谢物，包括精氨酸、组氨酸和甲硫氨酸。这些代谢物中的大多数不仅与多种污染物相关，而且在患有哮喘和没有哮喘的参与者之间表达差异。分析表明，这些代谢物共同参与了一个以精氨酸代谢为中心的相互关联的分子网络，这是交通相关污染物对哮喘患者影响的基础。我们检测到许多与通勤期间车内暴露相关的显著代谢紊乱，并验证了与几种炎症和氧化还原途径密切相关的代谢物，阐明与交通有关的空气污染毒性的潜在分子机制。这些结果支持未来交通暴露的代谢标志物和相应的分子机制的研究。
Background: Mechanisms underlying the effects of traffic-related air pollution on people with asthma remain largely unknown, despite the abundance of observational and controlled studies reporting associations between traffic sources and asthma exacerbation and hospitalizations.Objectives: To identify molecular pathways perturbed following traffic pollution exposures, we analyzed data as part of the Atlanta Commuters Exposure (ACE-2) study, a crossover panel of commuters with and without asthma.Methods: We measured 27 air pollutants and conducted high-resolution metabolomics profiling on blood samples from 45 commuters before and after each exposure session. We evaluated metabolite and metabolic pathway perturbations using an untargeted metabolome-wide association study framework with pathway analyses and chemical annotation.Results: Most of the measured pollutants were elevated in highway commutes (p < 0.05). From both negative and positive ionization modes, 17,586 and 9087 metabolic features were extracted from plasma, respectively. 494 and 220 unique features were associated with at least 3 of the 27 exposures, respectively (p < 0.05), after controlling confounders and false discovery rates. Pathway analysis indicated alteration of several inflammatory and oxidative stress related metabolic pathways, including leukotriene, vitamin E, cytochrome P450, and tryptophan metabolism. We identified and annotated 45 unique metabolites enriched in these pathways, including arginine, histidine, and methionine. Most of these metabolites were not only associated with multiple pollutants, but also differentially expressed between participants with and without asthma. The analysis indicated that these metabolites collectively participated in an interrelated molecular network centering on arginine metabolism, underlying the impact of traffic-related pollutants on individuals with asthma.Conclusions: We detected numerous significant metabolic perturbations associated with in-vehicle exposures during commuting and validated metabolites that were closely linked to several inflammatory and redox pathways, elucidating the potential molecular mechanisms of traffic-related air pollution toxicity. These results support future studies of metabolic markers of traffic exposures and the corresponding molecular mechanisms.