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

Particle and Fibre Toxicology

Yanbo Li¹  Xinying Zhao¹  Zhiwei Sun¹  Rui Chen¹  Xuejing Sun²  Caixia Guo²  Yi Qi²  Ru Ma²  Piye Niu²  Xueyan Li² 

[1] Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, 100069, Beijing, China;Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, 100069, Beijing, China;Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, 100069, Beijing, China;Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, 100069, Beijing, China;

关键词: Silica nanoparticles;    Atherosclerosis;    Foam cell;    Endoplasmic reticulum stress;    CD36;   

DOI  :  10.1186/s12989-020-00380-0

来源: Springer

【 摘 要 】

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

【 授权许可】

CC BY