circRNAs deregulation in exosomes derived from BEAS-2B cells is associated with vascular stiffness induced by PM_2.5

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 mRNAs (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_0053261 and 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.