Air Pollution Exposure Induces Vascular Endothelial Cell Dysfunction via Elevated Circulating F2: Multiomics Insights from an Ex Vivo Biosensor Assay.

Air pollution-induced cardiovascular disease is a leading contributor to the increasing global disease burden. Disruption of vascular endothelial function is a central driver of disease onset; however, the systemic mechanisms linking pollution exposure to endothelial dysfunction remain poorly defined. Here, we investigated early molecular responses to short-term exposure via integrated proteomic, metabolomic, and transcriptomic analyses. In a panel study of eight college students traveling from Qingdao to Shijiazhuang, China, where PM2.5, PM10, SO2, NO2, and CO levels were substantially higher, we collected serum samples at multiple time points and assessed endothelial responses via ex vivo biosensors. Proteomic profiling revealed the activation of hemostasis-related processes with interaction network analysis identifying F2 (prothrombin) as a central node strongly correlated with pollutant exposure. Metabolomic analysis revealed significant perturbations in bile acid biosynthesis and arginine-proline metabolism, with PM2.5-associated metabolites predominantly enriched in energy metabolism-related pathways. Transcriptomic profiling of endothelial cells provided further corroborating evidence that acute exposure to ambient air pollutants is capable of triggering endothelial cell activation. Subsequent weighted gene coexpression network analysis identified F2 as a pivotal molecular mediator underlying air pollutant-induced endothelial dysfunction. Together, these findings delineate the molecular architecture of acute pollution-induced endothelial cell dysfunction and identify F2-centered pathways as potential early targets for mitigating cardiovascular toxicity.