Ambient fine particulate matter aggravates atherosclerosis in apolipoprotein E knockout mice by iron overload via the hepcidin-ferroportin axis.

AIMS:Exposure to fine particulate matter (PM2.5) is correlated to atherosclerosis, but the mechanism remains largely undefined. Iron overload is a significant contributor to atherosclerosis, and iron homeostasis is highly regulated by the hepcidin-ferroportin (FPN) axis. Here we aimed to investigate the association between iron overload and PM2.5-induced atherosclerotic mice. MAIN METHODS:Apolipoprotein E knockout (ApoE-/-) mice were randomly assigned to filtered air (FA group) or PM2.5 (PM2.5 group) for 3-month inhalation. Daily PM2.5 mass concentrations, serum levels of ferritin, iron, pro-atherosclerotic cytokines and lipid profiles, atherosclerotic lesion areas, hepcidin, FPN and iron depositions in atherosclerotic lesions, hepcidin, FPN mRNA and protein expressions in the aorta were detected, respectively. KEY FINDINGS:The daily average concentration of atmospheric PM2.5 was 68.2 ± 21.8 μg/m3. Serum levels of ferritin, iron, VEGF, MCP-1, IL-6, TNF-α, TC and LDL-C, atherosclerotic lesion areas, hepcidin and iron depositions in atherosclerotic lesions, hepcidin mRNA and protein expressions in the PM2.5 group were observably higher than those in the FA group. Nevertheless, FPN deposition in atherosclerotic lesions, FPN mRNA and protein expressions in the aorta of the PM2.5 group were markedly lower than those of the FA group. SIGNIFICANCE:PM2.5 inhalation could exacerbate the formation and development of atherosclerosis in ApoE-/- mice, the potential mechanisms may be partly associated with iron overload via the hepcidin-FPN axis, as well as iron-triggered systemic inflammation and hyperlipidemia.