Effects of Exposure to Ambient Air Pollution on Human Metabolome in Patients with Coronary Artery Disease

Despite the established associations between air pollution and cardiovascular diseases (CVD), the biological mechanisms underlying its toxic effects remain largely unknown. We investigated whether exposure to both short- and long-term ambient air pollutants is associated with systemic perturbations in the human metabolome. Using a metabolome-wide association (MWAS) study framework with pathway enrichment and chemical annotation, we analyzed plasma samples from 244 patients with coronary artery disease (CAD) in the Emory Cardiovascular Biobank cohort. Individual residential exposures to air pollutants carbon monoxide (CO), nitrogen oxides (NO_<i>x</i>), and fine particulate matter (PM_2.5) were estimated across four exposure time windows (1-day, 1-week, 1-month, and-1 year) using a spatiotemporal model. High-resolution metabolomics identified 33 pathways indicative of perturbations in the metabolism of amino acids, carbohydrate/glycan, coenzyme/vitamin, and lipids. Thirty-eight unique metabolites were associated with NO_<i>x</i> and PM_2.5 under different exposure time windows, including protoporphyrin, thyroxine, methyl beta-d-galactoside, lauroylcarnitine, retinoate, and bis(2-ethylhexyl)phthalate (DEHP). The observed metabolic perturbations are closely linked to energy metabolism, inflammation, and redox homeostasis, revealing potential differential effects of air pollution exposure on the human metabolome under varying exposure durations and offering important insights for future biomarker development and investigation of molecular mechanisms for air pollution effects on CVD.