Metabolomic assessment of exposure to near-highway ultrafine particles

• Type of Material: Article
• Authors: Douglas Walker, Emory University; Kevin J. Lane, Boston University; Ken Liu, Emory University; Karan Uppal, Emory University; Allison P. Patton, Health Effects Institute; John L. Durant, Tufts University; Dean P Jones, Emory University; Doug Brugge, Tufts University; Kurt D. Pennell, Tufts University
• Language: English
• Date: 2018-01-01
• Publisher: Springer Nature [academic journals on nature.com]: Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018, Springer Nature America, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1038/s41370-018-0102-5
• Title of Journal or Parent Work: Journal of Exposure Science and Environmental Epidemiology
• ISSN: 1559-0631
• Volume: 29
• Issue: 4
• Start Page: 469
• End Page: 483
• Grant/Funding Information: This work was supported by funds received from the National Institute of Health, award numbers ES019776, ES023485, ES025632, ES015462 and 0D018006.
• Keywords: High-resolution metabolomics; Metabolome-wide association study; Traffic-related air pollution; Exposome
• Research Categories: Health Sciences, Medicine and Surgery; Engineering, Environmental; Environmental Sciences

Abstract

Exposure to traffic-related air pollutants has been associated with increased risk of adverse cardiopulmonary outcomes and mortality; however, the biochemical pathways linking exposure to disease are not known. To delineate biological response mechanisms associated with exposure to near-highway ultrafine particles (UFP), we used untargeted high-resolution metabolomics to profile plasma from 59 participants enrolled in the Community Assessment of Freeway Exposure and Health (CAFEH) study. Metabolic variations associated with UFP exposure were assessed using a cross-sectional study design based upon low (mean 16,000 particles/cm3) and high (mean 24,000 particles/cm3) annual average UFP exposures. In comparing quantified metabolites, we identified five metabolites that were differentially expressed between low and high exposures, including arginine, aspartic acid, glutamine, cystine and methionine sulfoxide. Analysis of the metabolome identified 316 m/z features associated with UFP, which were consistent with increased lipid peroxidation, endogenous inhibitors of nitric oxide and vehicle exhaust exposure biomarkers. Network correlation analysis and metabolic pathway enrichment identified 38 pathways and included variations related to inflammation, endothelial function and mitochondrial bioenergetics. Taken together, these results suggest UFP exposure is associated with a complex series of metabolic variations related to antioxidant pathways, in vivo generation of reactive oxygen species and processes critical to endothelial function.