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

Abstract

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.

• Authors: Yongheng Gao, Qian Zhang, Jinbo Sun, Yuan Liang, Minlong Zhang, Mingxuan Zhao, Kailiang Zhang, Chuan Dong, Qiong Ma, Wei Liu, Wangping Li, Yanwei Chen, Luyao Han, Faguang Jin
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 36 Issue 2 Pg. e22161 (02 2022) ISSN: 1530-6860 [Electronic] United States
• PMID: 35061300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

Chemical References

• Apoe protein, mouse
• Apolipoproteins E
• Particulate Matter

Topics

• Alveolar Epithelial Cells (drug effects, metabolism, pathology)
• Animals
• Aorta (drug effects, metabolism, physiology)
• Apolipoproteins E (metabolism)
• Atherosclerosis (metabolism, pathology)
• Cell Adhesion (drug effects)
• Endothelium (drug effects, metabolism, pathology)
• Extracellular Vesicles (drug effects, metabolism, pathology)
• Mice
• Particulate Matter (adverse effects)
• Plaque, Atherosclerotic (metabolism, pathology)
• RAW 264.7 Cells
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)