摘要
As an environmental pollutant,ambient fine particulate matter (PM_(2.5)) was linked to cardiovascular diseases.The molecular mechanisms underlying PM_(2.5)-induced extrapulmonary disease has not been elucidated clearly.In this study the ambient PM_(2.5)exposure mice model we established was to explore adverse effects of vessel and potential mechanisms.Long-term PM_(2.5)exposure caused reduced lung function and vascular stiffness in mice.And chronic PM_(2.5)induced migration and epithelial-mesenchymal transition (EMT) phenotype in BEAS-2B cells.After PM_(2.5)treatment,the circRNAs and mRNAs levels of exosomes released by BEAS-2B cells were detected by competing endogenous RNA (ceRNA) array,which contained 1664 differentially expressed circRNAs (DE-circRNAs) and 308 differentially expressed m RNAs (DE-mRNAs).By bioinformatics analysis on host genes of DE-circRNAs,vascular diseases and some pathways related to vascular diseases including focal adhesion,tight junction and adherens junction were enriched.Then,ceRNA network was constructed,and DE-mRNAs in ceRNA network were conducted functional enrichment analysis by Ingenuity Pathway Analysis,which indicated that hsa_circ_0012627,hsa_circ_0053261and hsa_circ_0052810 were related to vascular endothelial dysfunction.Furthermore,it was verified experimentally that Exo^(PM2.5)could induce endothelial dysfunction by increased endothelial permeability and decreased relaxation in vitro.In present study,we investigated in-depth knowledge into the molecule events related to PM_(2.5) toxicity and pathogenesis of vascular diseases.
基金
supported by the National Natural Science Foundation of China (Nos. 92043202, 91643108, and 81973074)
Foundation by Science and Technology Project of Hebei Education Department (No. QN2020175)。
