Extracellular vesicles derived from PM2.5-exposed alveolar epithelial cells mediate endothelial adhesion and atherosclerosis in ApoE-/- mice

Epidemiological studies suggested that PM2.5 (particle matters with an aerodynamic diameter <= 2.5 mu m) exposure is associated with atherosclerosis. Extracellular vesicles (EVs) are messengers between intracellular communications which are important in diseases procession. At present, whether EVs derived from PM2.5-exposed alveolar epithelial cells (P-EVs) involve in atherosclerosis has not been clearly understood. This study is performed to investigate the effects of P-EVs on the development of endothelium adhesion and atherosclerosis. Here, ApoE(-/-) mice were randomized into different groups receiving one of the following treatments, filtered air (FA), PM2.5, PBS, PBS-treated alveolar epithelial cells-derived EVs (EVs), or P-EVs. Then the atherosclerosis level in aortas or aorta sections was evaluated by oil red O staining. The results indicated that ApoE(-/-) mice treated with P-EVs or PM2.5 showed more obvious atherosclerosis plaques in aortas and aortic arches than those treated with EVs or PBS. Endothelial cells (ECs) were treated with PBS, EVs, P-EVs, or PM2.5. The adhesion property, miRNAs level and expressions of I kappa B alpha, phosphorylated I kappa B alpha, NF-kappa B p65, phosphorylated NF-kappa B p65, and VCAM1 in ECs were determined. It was found that P-EVs activated I kappa B alpha-NF-kappa B-VCAM1 signaling and increased adhesion of ECs, and such effects could be reversed by adalimumab (the TNF-alpha inhibitor) or miR-326-3p inhibitor. Further study suggested that P-EVs induced upregulation of TNF-alpha and miR-326-3p in recipient ECs and contributed to the phosphorylation of NF-kappa B p65. Collectively, EVs derived from PM2.5-exposed alveolar epithelial cells played an important role in the development of atherosclerosis via activating I kappa B alpha-NF-kappa B-VCAM1 signaling.

Automated summary

Extracellular vesicles derived from PM2.5-exposed alveolar epithelial cells play a significant role in the development of atherosclerosis by activating the I kappa B alpha-NF-kappa B-VCAM1 signaling pathway and increasing the adhesion of endothelial cells.