Circulatory Molecular Atlas Reveals Dose- and Time-dependent Perturbation and Recovery Signatures after Acute PM2.5 Exposure

Recent epidemiological and toxicological studies have linked exposure to ambient fine particulate matter (PM2.5) to various diseases and adverse health outcomes. However, a comprehensive atlas of the molecular responses and underlying mechanisms that connect PM2.5 exposure to long-term effects remains elusive. To bridge this gap, we established a dose- and time-dependent serum multiomics atlas in mice following a single PM2.5 exposure by integrating biochemical indexes and proteomic, metabolomic, and lipidomic profiles collected at 3, 7, 14, and 21 days postexposure across 10, 50, and 150 μg doses. Across increasing PM2.5 doses, systemic perturbations progressed from mild inflammatory activation to coordinated disruptions of hemostasis and metabolic homeostasis. Over time, trajectories shifted from acute injury and immune mobilization (3–7 days) to later metabolic remodeling and tissue repair (14–21 days). Multiomics integrative analyses revealed early hemostatic and inflammatory perturbations with later recovery processes, outlining a continuum from acute insult to long-term effects. This work provides novel mechanistic insights into the systemic pathophysiology of air pollution, establishing a foundation for elucidating the molecular transitions that link acute exposure to chronic health risks.