The Differences Between Action of Inhaled Silica and Iron Nanoparticles in ApoE-knockout mice – Silica Nanoparticles Exacerbate Atherosclerosis Through Skewing Macrophage Polarization Towards M1 Phenotype

Abstract Background: Exposure to airborne particulate matter, especially its organic part, is strongly related to the development of cardiovascular disorders including atherosclerosis. The role of inorganic part of air pollution in the pathogenesis of atherosclerosis is still unclear. The aim of this study was to investigate the mechanism of action of two substantial components of inorganic part of airborne particulate matter (SiO2 and Fe2O3) in atherosclerosis. To do this, we used apolipoprotein E-knockout mice exposed to silica (SiNPs) and ferric oxide (FeNPs) nanoparticles in a whole body inhalation chamber for 16 weeks. To our knowledge, this is the first time when whole body exposure system was applied to examine the effects of silica and ferric oxide nanoparticles on atherosclerosis development in mouse model of atherosclerosis. Results: Inhaled silica nanoparticles augmented the atherosclerotic lesions and increased the percentage of pro-inflammatory M1 macrophages in both the plaque and the peritoneum in apoE-/- mice. Exposure to ferric oxide nanoparticles did not enhance atherogenesis process, however, it caused significant changes in the atherosclerotic plaque composition (elevated content of CD68-positive macrophages and enlarged necrotic core accompanied by the decreased level of M1 macrophages). Both silica and iron oxide NPs altered the phenotype of T lymphocytes in the spleen by promoting polarization towards Th17 cells. Conclusions: Exposure to silica and ferric oxide nanoparticles exerts differential impact on atherosclerosis development. Silica nanoparticles enhance atherosclerosis, which is associated with increased level of M1 macrophages, while ferric oxide nanoparticles alter atherosclerotic plaque composition without influencing the size of the lesions.