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
Highlights
The rapid development and enormous progress in nanotechnology bring the toxicological concerns to nanomaterials (NMs), which might pose potential threats to human health and the environment
Arterial stiffness was reported to be positively correlated with reactive oxygen species (ROS) and the followed oxidative stress [34], which was commonly regarded as a major attributor of the adverse effects caused by SiNPs [35]
The phenomena mentioned above was significantly manifested in the SiNPs group with a higher dose (6.0 mg/ kg·bw), which was closely associated with the exposure mode
Summary
The rapid development and enormous progress in nanotechnology bring the toxicological concerns to nanomaterials (NMs), which might pose potential threats to human health and the environment. Silica nanoparticles (SiNPs) rank in the top two global productions in NMs, with an annual output of nearly 1.5 million tons [1] It has a wide range of applications for industrial products and consumers, such as food additive, surfactants, catalysts, sensors, ceramics, paints, and for medical and biomedical fields, e.g., drug delivery, disease diagnosis and treatment [2, 3]. Such mass production and widespread application of SiNPs would inevitably increase human exposure via occupational, environmental or even iatrogenic ways. Thereby, this study aimed to explore the effects of SiNPs on the progression of atherosclerosis, and to investigate related mechanisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
