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.
Keywords: Exposome; High-resolution metabolomics; Metabolome-wide association study; Traffic-related air pollution.