Lipid accumulation in multi-walled carbon nanotube-exposed HepG2 cells: Possible role of lipophagy pathway

et al. 2020

Part Fibre Toxicol

Background 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. Results 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. Conclusions 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. Graphical abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

Part Fibre Toxicol

“…Therefore, ER stress is likely to be the key factor for NPs and their cardiovascular effects. However, most existing studies on NPs focus on the ER stress-mediated apoptosis process [67], and only a few studies found that ER stress induced by NPs may be involved in regulating cellular lipid metabolism [43,68].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

Preprint

Background: 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. Results: 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 by SiNPs. Conclusions: 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.

“…It is worth noting that some ER stress genes are involved in lipid metabolism, which fuel atherogenesis. For instance, CHOP is crucial for lipid synthesis, and its expression would result in lipid accumulation [71]. The cellular lipid homeostasis is highly, precisely regulated by lipid in ux and e ux.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

Preprint

Abstract Background: 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 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. Results: 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. Histopathological investigation reflected a greater plaque burden in the aortic root of SiNPs-exposed ApoE -/- mice. When compared to the control, 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 by SiNPs. Conclusions: 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.