Abohashem S, Osborne MT, Dar T, et al. - Among humans, this inquiry was conducted to determine if there exists an association of PM_2.5 ( particulate matter with diameter < 2.5 μm) with higher leucopoietic tissue activity and arterial inflammation (ArtI), and if these links persisted following accounting for the impacts of potential confounders including socioeconomics, traffic noise, and risk factors, and if these tissue impacts mediate the connection between air pollution and major adverse cardiovascular events (MACE). This analysis involved people (N = 503) without cardiovascular disease (CVD) or active cancer. A link of higher PM_2.5 with increased leucopoietic activity as well as ArtI was identified at baseline, after adjusting for CVD risk factors. A link was also found between PM_2.5 exposure and MACE, which continued to be significant following adjustment for CVD risk factors and other potential confounders. In mediation analysis, the association between PM_2.5 exposure and MACE was shown to be serially mediated by increased leucopoietic activity and ArtI. Overall, findings demonstrated an association of higher air pollution exposure with heightened leucopoietic activity and ArtI and also revealed an independent prediction of MACE by higher air pollution exposure via a biological pathway that involves higher leucopoietic activity and ArtI in series.