当前位置: X-MOL 学术Part. Fibre Toxicol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in ApoE−/− mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2020-10-02 , DOI: 10.1186/s12989-020-00380-0
Ru Ma 1, 2 , Yi Qi 1, 2 , Xinying Zhao 2, 3 , Xueyan Li 1, 2 , Xuejing Sun 1, 2 , Piye Niu 1, 2 , Yanbo Li 2, 3 , Caixia Guo 1, 2 , Rui Chen 2, 3 , Zhiwei Sun 2, 3
Affiliation  

The 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. We 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. Our 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.

中文翻译:

无定形二氧化硅纳米颗粒通过内质网应激介导的巨噬细胞CD36上调加速了ApoE -/-小鼠的动脉粥样硬化病变进程

二氧化硅纳米颗粒(SiNPs)的生物安全问题随着其大规模生产和广泛应用而迅速扩大。SiNPs暴露对心血管的影响已逐渐得到证实,但是,SiNPs暴露与动脉粥样硬化之间的相互作用以及潜在的机制仍然未知。因此,本研究旨在探讨SiNPs对动脉粥样硬化进展的影响,并研究相关机制。我们首先通过气管内滴注以西方饮食喂养的ApoE-/-小鼠研究了SiNPs暴露对动脉粥样硬化的体内影响。超声显微镜显示,与对照组相比,脉搏波速度(PWV)显着增加,并且组织病理学研究表明,暴露于SiNPs的ApoE-/-小鼠的主动脉根中斑块负荷更大。与对照组相比,SiNPs暴露后血清总甘油三酸酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平升高。此外,SiNPs暴露后斑块中发生了巨噬细胞浸润和内质网(ER)应激,CD68和CHOP表达上调证明了这一点。进一步在体外,证实SiNPs激活ER应激并诱导小鼠巨噬细胞RAW264.7中的脂质蓄积。机理分析表明,4-PBA(一种经典的ER应激抑制剂)预处理可大大减轻SiNPs诱导的巨噬细胞脂质蓄积,并逆转SiNPs诱导的CD36表达升高。我们的研究结果首先揭示了SiNPs对ApoE-/-小鼠动脉粥样硬化进展的促进作用,
更新日期:2020-10-02
down
wechat
bug