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Extracellular vesicles derived from PM2.5‐exposed alveolar epithelial cells mediate endothelial adhesion and atherosclerosis in ApoE −/− mice
Author(s) -
Gao Yongheng,
Zhang Qian,
Sun Jinbo,
Liang Yuan,
Zhang Minlong,
Zhao Mingxuan,
Zhang Kailiang,
Dong Chuan,
Ma Qiong,
Liu Wei,
Li Wangping,
Chen Yanwei,
Han Luyao,
Jin Faguang
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100927rr
Subject(s) - chemistry , oil red o , microbiology and biotechnology , downregulation and upregulation , extracellular vesicles , apolipoprotein e , inflammation , adhesion , exosome , microvesicles , immunology , medicine , biology , microrna , in vitro , pathology , biochemistry , disease , gene , adipogenesis , organic chemistry
Epidemiological studies suggested that PM2.5 (particle matters with an aerodynamic diameter ≤2.5 μm) 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 IκBα, phosphorylated IκBα, NF‐κB p65, phosphorylated NF‐κB p65, and VCAM1 in ECs were determined. It was found that P‐EVs activated IκBα‐NF‐κB‐VCAM1 signaling and increased adhesion of ECs, and such effects could be reversed by adalimumab (the TNF‐α inhibitor) or miR‐326‐3p inhibitor. Further study suggested that P‐EVs induced upregulation of TNF‐α and miR‐326‐3p in recipient ECs and contributed to the phosphorylation of NF‐κB p65. Collectively, EVs derived from PM2.5‐exposed alveolar epithelial cells played an important role in the development of atherosclerosis via activating IκBα‐NF‐κB‐VCAM1 signaling.