circRNAs deregulation in exosomes derived from BEAS-2B cells is associated with vascular stiffness induced by PM2.5
Rong Zhang , Qingping Liu , Yaling Zhang , Bin Han , Mengruo Wang , Huaifang Hu , Jie Ning , Wentao Hu , Meiyu Chen , Yaxian Pang , Yuanyuan Chen , Lei Bao , Yujie Niu
DOI:10.1016/j.jes.2023.02.027
Received November 18, 2022,Revised , Accepted February 15, 2023, Available online February 24, 2023
Volume 36,2024,Pages 527-539
As an environmental pollutant, ambient fine particulate matter (PM2.5) was linked to cardiovascular diseases. The molecular mechanisms underlying PM2.5-induced extrapulmonary disease has not been elucidated clearly. In this study the ambient PM2.5 exposure mice model we established was to explore adverse effects of vessel and potential mechanisms. Long-term PM2.5 exposure caused reduced lung function and vascular stiffness in mice. And chronic PM2.5 induced migration and epithelial-mesenchymal transition (EMT) phenotype in BEAS-2B cells. After PM2.5 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 ExoPM2.5 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 PM2.5 toxicity and pathogenesis of vascular diseases.
