Proteomics reveals how air pollutants drive chronic disease

In 48,645 UK Biobank participants, researchers profiled plasma proteins associated with four ambient air pollutants: fine particulate matter (PM2.5), coarse particulate matter (PM10), nitrogen dioxide, and nitrogen oxides. They examined associations between these proteomic signatures, overall mortality, and risks of major chronic diseases. Proteins jointly linked to all four pollutants were enriched in immune regulatory pathways. Unique signatures emerged for specific pollutants: vascular dysfunction for PM2.5, DNA damage for PM10, apoptosis signaling for nitrogen dioxide, and extracellular matrix remodeling for nitrogen oxides. Mediation and Mendelian randomization analyses identified causal mediating proteins tied to outcomes, revealing shared inflammatory mechanisms alongside outcome-specific pathways, including vascular remodeling for cardiovascular disease, oxidative stress for chronic kidney disease, and cell adhesion for dementia. Additionally, advanced glycosylation end product-specific receptor (AGER) showed specificity for chronic respiratory disease and lung cancer.