PM_2.5 promotes platelet activation and thrombosis via ROS/MAPKs pathway-mediated mitochondrial dysfunction

Particulate matter (PM_2.5) has been identified as a significant risk factor for the development of cardiovascular disease. The current work combined a human panel study with animal experiments intended to investigate the effects of ambient PM_2.5 on platelet function and tried to figure out the potential mechanisms. The results showed that inhaling PM_2.5 caused platelet aggregation in both human subjects and mouse models, resulting in changes to both the quantity and function of platelets. The multi-omics analysis showed that platelets stimulated by PM_2.5 reduce the expression of the mitochondrial complex IV subunit cytochrome c oxidase subunit 1 (mt-COX1). In addition, PM_2.5 may lead to an increase in platelet ROS, which activates the mitogen-activated protein kinases (MAPKs) pathway thereby promoting platelet activation and thrombosis. The antioxidant N-acetyl-L-cysteine (NAC) is found to reverse these changes in vitro. In conclusion, the present study provides evidence that exposure to ambient PM_2.5 is associated with thrombosis by directly impairing platelet function, in which ROS/MAPKs pathway may be the potential target.