Exposure to ambient fine particulate matter (<2.5 μm; PM2.5) increases the risk of the physiopathology of vascular diseases. However, the underlying mechanism, particularly the mitochondrial damage mechanism, of PM2.5‐induced vascular dysfunction is still unclear. In this study, we examined PM2.5‐induced alterations of mitochondrial morphology, and further demonstrated the adverse effects on mitochondrial dynamics and function in vascular endothelial cells. Consequently, cultured EA.hy926 cells were subjected to PM2.5 collected from Beijing. A Cell Counting Assay Kit‐8 demonstrated that PM2.5 exposure decreased the proliferation of EA.hy926 cells in a dose‐dependent manner. The exposure caused an increment of abnormal mitochondria coupled with the decrease of fusion protein MFN2 and the increase of fission protein FIS1, suggesting that PM2.5 inhibits mitochondrial fusion. Further analyses revealed PM2.5 decreased the mitochondrial membrane potential (ΔΨm) and increased the mitochondrial permeability transport pore opening, eventually resulting in impairments in adenosine triphosphate synthesis. Therefore, it is clearly shown that PM2.5 triggered endothelial toxicity through mitochondria as the target, including the damage of mitochondrial homeostasis.

Epidemiological studies have corroborated that respiratory diseases, including lung cancer, are related to fine particulate matter (<2.5 μm) (PM2.5) exposure. The toxic responses of PM2.5 are greatly influenced by the source of PM2.5. However, the effects of PM2.5 from Beijing on bronchial genotoxicity are scarce. In the present study, PM2.5 from Beijing was sampled and applied in vitro to investigate its genotoxicity and the mechanisms behind it. Human bronchial epithelial cells 16HBE were used as a model for exposure. Low (67.5 μg/mL), medium (116.9 μg/mL), and high (202.5 μg/mL) doses of PM2.5 were used for cell exposure. After PM2.5 exposure, cell viability, oxidative stress markers, DNA (deoxyribonucleic acid) strand breaks, 8-OH-dG levels, micronuclei formation, and DNA repair gene expression were measured. The results showed that PM2.5 significantly induced cytotoxicity in 16HBE. Moreover, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and cellular heme oxygenase (HO-1) were increased, and the level of glutathione (GSH) was decreased, which represented the occurrence of severe oxidative stress in 16HBE. The micronucleus rate was elevated, and DNA damage occurred as indicators of the comet assay, γ-H2AX and 8-OH-dG, were markedly enhanced by PM2.5, accompanied by the influence of 8-oxoguanine DNA glycosylase (OGG1), X-ray repair cross-complementing gene 1 (XRCC1), and poly (ADP-ribose) polymerase-1 (PARP1) expression. These results support the significant role of PM2.5 genotoxicity in 16HBE cells, which may occur through the combined effect on oxidative stress and the influence of DNA repair genes.

No abstract

No abstract

No abstract