Multi-organ toxicity caused by PM2.5 in mice with cardiovascular diseases: The role of PAHs played from the most polluted episodes in China.

PAHs pollutants, as the key toxic components in PM_2.5, have been proved to be closely related to the morbidity and mortality of people with cardiovascular diseases, however, their effects on organs and tissues other than cardiovascular/lung systems have not been deeply discussed. Here we collected PM_2.5 samples from 2017 to 2020 in Xi'an, the city with one of the highest PM_2.5 level in China, investigated the effects of PM_2.5-bound PAHs on lung, spleen, liver and kidney by using the ApoE^-/- mice model with high-fat diet. Firstly, six key toxic components in PAHs were screened to determine their relative importance in pollutants. The results showed that PAHs had the most significant toxicity in lung, followed by liver, kidney and spleen. In addition, PAHs activated systemic inflammation by enhancing the production of IL-6, particularly through strong protein interactions, mainly via van der Waals forces. This process exacerbated cardiovascular damage and led to elevated levels of pro-inflammatory cytokines circulating in the bloodstream, thereby increasing multi-organ toxicity. The results of this study deepened the understanding of comprehensive impacts of PAHs on cardiovascular patients, and suggest more strict emission source-control strategies on PAHs prevention especially for the susceptible population with cardiovascular diseases.