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Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in ApoE−/− mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage

Authors
  • Ma, Ru1, 1
  • Qi, Yi1, 1
  • Zhao, Xinying1, 1
  • Li, Xueyan1, 1
  • Sun, Xuejing1, 1
  • Niu, Piye1, 1
  • Li, Yanbo1, 1
  • Guo, Caixia1, 1
  • Chen, Rui1, 1
  • Sun, Zhiwei1, 1
  • 1 Capital Medical University, Beijing, 100069, China , Beijing (China)
Type
Published Article
Journal
Particle and Fibre Toxicology
Publisher
BioMed Central
Publication Date
Oct 02, 2020
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12989-020-00380-0
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundThe biosafety concern of silica nanoparticles (SiNPs) is rapidly expanding alongside with its mass production and extensive applications. The cardiovascular effects of SiNPs exposure have been gradually confirmed, however, the interaction between SiNPs exposure and atherosclerosis, and the underlying mechanisms still remain unknown. Thereby, this study aimed to explore the effects of SiNPs on the progression of atherosclerosis, and to investigate related mechanisms.ResultsWe firstly investigated the in vivo effects of SiNPs exposure on atherosclerosis via intratracheal instillation of ApoE−/− mice fed a Western diet. Ultrasound microscopy showed a significant increase of pulse wave velocity (PWV) compared to the control group, and the histopathological investigation reflected a greater plaque burden in the aortic root of SiNPs-exposed ApoE−/− mice. Compared to the control group, the serum levels of total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were elevated after SiNPs exposure. Moreover, intensified macrophage infiltration and endoplasmic reticulum (ER) stress was occurred in plaques after SiNPs exposure, as evidenced by the upregulated CD68 and CHOP expressions. Further in vitro, SiNPs was confirmed to activate ER stress and induce lipid accumulation in mouse macrophage, RAW264.7. Mechanistic analyses showed that 4-PBA (a classic ER stress inhibitor) pretreatment greatly alleviated SiNPs-induced macrophage lipid accumulation, and reversed the elevated CD36 expression induced by SiNPs.ConclusionsOur results firstly revealed the acceleratory effect of SiNPs on the progression of atherosclerosis in ApoE−/− mice, which was related to lipid accumulation caused by ER stress-mediated upregulation of CD36 expression in macrophage.Graphical abstract

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