Circulatory Molecular Atlas Reveals Dose- and Time-dependent Perturbation and Recovery Signatures after Acute PM_2.5...

Area of Science:

• Environmental Health
• Toxicology
• Molecular Biology

Background:

• Epidemiological studies link ambient fine particulate matter (PM2.5) exposure to adverse health outcomes.
• Mechanistic understanding of PM2.5's long-term health effects requires a comprehensive molecular atlas.

Purpose of the Study:

• To create a dose- and time-dependent serum multiomics atlas in mice after PM2.5 exposure.
• To elucidate the molecular mechanisms connecting PM2.5 exposure to long-term health risks.

Main Methods:

• Integrated biochemical, proteomic, metabolomic, and lipidomic profiling in mice.
• Single PM2.5 exposure at varying doses (10, 50, 150 μg) and time points (3, 7, 14, 21 days).

Main Results:

• Systemic perturbations progressed from inflammation to disruptions in hemostasis and metabolic homeostasis with increasing PM2.5 dose.
• Temporal analysis showed a shift from acute injury and immune response (3-7 days) to metabolic remodeling and repair (14-21 days).
• Multiomics integration identified early hemostatic/inflammatory changes and later recovery processes.

Conclusions:

• This study provides a multiomics atlas detailing the systemic molecular response to PM2.5 exposure in mice.
• It reveals a continuum from acute air pollution insult to long-term effects, offering mechanistic insights into pathophysiology.
• The findings establish a foundation for understanding molecular transitions linking acute exposure to chronic health risks.