New mechanisms of PM2.5 induced atherosclerosis: Source dependent toxicity and pathogenesis

Exposure to fine particulate matter (PM_2.5) is recognized to induce atherosclerosis, but the underlying mechanisms are not fully understood. This study used ambient PM_2.5 samples collected in one of the highly polluted regions of Guanzhong Plain in China (2017–2020) and an ApoE^−/− mouse model to investigate the association between exposure to PM_2.5 and atherosclerosis. Despite a substantial decrease in the ambient concentration of PM_2.5 from 266.7 ± 63.9 to 124.4 ± 37.7 μg m⁻³ due to the execution of a series of emission controls, cardiovascular toxicity due to exposure to PM_2.5 remained at a significantly high level compared with the Control group. Moreover, the result highlighted that biomass burning (BB) showed an increased contribution to PM_2.5 while most anthropogenic sources decreased. This study found that PM_2.5 exposure led to vascular oxidative stress and inflammation, accelerated atherosclerotic plaque growth, and altered vascular proliferation pathways. The latter two mechanisms provide new insights into how PM_2.5 enhanced the processes of atherosclerosis, promoted lipoprotein cholesterol (LDL-C) absorption in vascular cells, and directed stimulation of cell function factors (VEGF and MCP-1), which are highly associated by PI3K/AKT signaling pathway. Polycyclic aromatic hydrocarbons (PAHs) and their derivatives, and certain biomarkers showed strong correlations with bio-reactivity, while BB was identified as a major contributor to toxicity of PM_2.5. The findings offer new insights into the role of PM_2.5 promoting atherosclerosis and provide recommendations for controlling PM_2.5 pollution to prevent and treat the disease particularly for susceptible populations.