| In recent years, air pollution is becoming a serious problem in Beijing, which has triggered widespread concern in the society. Particulate matter, the main environmental pollution, has seriously affected the people's daily life and health. As an important part of particulate matter, PM2.5 has become an important threat to human health.At present, a large number of epidemiological studies have shown that PM2.5 can cause the body's respiratory system and cardiovascular system diseases by entering the body through respiratory passage. Meanwhile, researchers found that the level of PM2.5 was closely related with the incidence of cancer.Based on current researches about how PM2.5 causes cardiovascular diseases,epidemiological studies have indicated that diseases such as hypertension and atherosclerosis were closely related with the inhalation concentration of PM2.5, and toxicology studies have shown that the occurrence of these diseases was associated with injury of vascular endothelial cells caused by PM2.5. However, specific toxicity mechanism of cardiovascular diseases such as atherosclerosis caused by PM2.5 isstill unknown. To further study the PM2.5's toxicity mechanism, the HUVEC cells were used to establish a cells model, and PM2.5 coming from Beijing in January 2014 was used to investigate the toxic effects of PM2.5 on HUVEC cells and related mechanism.At the same time, studies have suggested that Ah R is one of the possible mechanisms in which atherosclerosis was induced by environmental pollutants. To further study the mechanism based on the present findings, Ah R knockout lentivirus plasmid was constructed by the use of CRISPR-Cas9 system.The results in this paper showed a obviouscytotoxicity of the PM2.5 to HUVEC cells, and had a dose-effect relationship; cell micronucleus production rate could be increased by PM2.5, which could further speculate that PM2.5 may induce cell chromosome damage. The ultrastructural changes in HUVEC cells when cells exposed to PM2.5 were observed by using transmission electron microscope, and the results indicated that PM2.5 was present in the cytoplasm and nucleus and had caused changes in the structure of mitochondria. Furthermore, we also found that PM2.5 could induce autophagy, and then involved in toxic action of PM2.5 on cells to protect the cells. The results of gene expression spectrum detection showed that PM2.5 could induce the expression of genes related to inflammation, oxidative stress, and vasculardysfunction, the expression of Ah R and its target gene CYP1B1 were increased. The increased expression of HMOX1, as a key gene in oxidative stress, showed that HMOX1 played a critical role in resistance to PM2.5 damage. The increased expression of blood coagulation factor F3, which could be served as a marker of human cardiovascular injury caused by PM2.5,indicated PM2.5 inducing cardiovascular diseases such as atherosclerosis. Meanwhile, the signaling pathways such as cell p53 signaling pathway and NF-k B signaling pathway were also involved in the toxicity of PM2.5 to the HUVEC cells.Additionally, in this paper, CRISPR-Cas9 gene editing technology was used for constructing the Ah R knockout lentivirus plasmid, which provided an foundation for subsequent lentivirus packaging and studying the mechanism and function of Ah R in cardiovascular diseases especially such as atherosclerosis caused by PM2.5. |
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