Endoplasmic reticulum stress-dependent oxidative stress mediated vascular injury induced by silica nanoparticles in vivo and in vitro

Li, Yanbo; Ma, Ru; Li, Xiaoying; Qi, Yi; Abulikemu, Alimire; Zhao, Xinying; Duan, Huawei; Zhou, Xianqing; Guo, Caixia; Sun, Zhiwei

doi:10.1016/j.impact.2019.100169

Cited by 30 publications

(19 citation statements)

References 65 publications

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“…The induction of ER-associated UPR events by NPs was pointed out either in vitro or in vivo [38,61]. In particular, other than oxidative stress, ER stress was reported to mediate the SiNPs-caused vascular injury in rats [27]. To be noted, ER stress mediates cell apoptosis and lipid metabolism [62], and interacts with oxidative stress and autophagy, which are closely related to atherosclerosis [63,64].…”

Section: Discussionmentioning

confidence: 99%

“…So far, the effects of SiNPs on the formation and progression of atherosclerotic plaque is still poorly understood. Limited studies provided the vascular injury and dysfunction caused after SiNPs inhalation, probably associated with oxidative stress and inflammatory response [27]. In contrast, studies pointed out the good biological safety of SiNPs, which could improve the efficacy of cell therapy for myocardial infarction, and was considered the best candidate for stem cell therapy in cardiac tissue [28].…”

Section: Introductionmentioning

confidence: 99%

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

Zhao

et al. 2020

Part Fibre Toxicol

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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

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhao

et al. 2020

Part Fibre Toxicol

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“…Previously, SiNPs was con rmed to induce endothelial injury [36,[39][40][41] and promote the recruitment of monocytes to injured endothelial cells [42], and foam cell formation at the early stage of atherosclerosis [43]. Moreover, a discontinued or fragmented intimal surface was induced by repeated pulmonary exposure of SiNPs, accompanied with endothelial apoptosis [27]. In addition, the ability to induce thrombosis formation may also attribute to the pro-atherogenic potential of SiNPs [32].…”

Section: Discussionmentioning

confidence: 99%

“…The induction of ERassociated UPR events by NPs was pointed out either in vitro or in vivo [39,63]. In particular, other than oxidative stress, ER stress was reported to mediate the SiNPs-caused vascular injury in rats [27]. To be noted, ER stress mediates cell apoptosis and lipid metabolism [64], and interacts with oxidative stress and autophagy, which are closely related to atherosclerosis [65,66].…”

Section: Discussionmentioning

confidence: 99%

“…So far, whether SiNPs could cause the adverse effects on the formation and progression of atherosclerotic plaque is still poorly understood. Limited studies provided the vascular injury and dysfunction caused after SiNPs inhalation, probably associated with oxidative stress and in ammatory response [27]. In contrast, studies even pointed out that SiNPs with good biological safety, could improve the e cacy of cell therapy for myocardial infarction, and was considered the best candidate for stem cell therapy in cardiac tissue [28].…”

Section: Introductionmentioning

confidence: 99%

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

Zhao

et al. 2020

Preprint

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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.

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Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

Cao

2021

J of Applied Toxicology

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The development of nanotechnology leads to the exposure of human beings to nanomaterials (NMs), and there is a health concern about the adverse vascular effects of NMs. Current data from epidemiology, controlled human exposure, and animal studies suggested that exposure to NMs could induce cardiopulmonary effects. In support of in vivo findings, in vitro studies showed that direct contact of vascular cells with NMs could induce endothelial cell (EC) activation and promote macrophage foam cell formation, although only limited studies showed that NMs could damage vascular smooth muscle cells and promote their phenotypic switch. It has been proposed that NMs induced adverse vascular effects via different mechanisms, but it is still necessary to understand the upstream events. Kruppel‐like factors (KLFs) are a set of C2H2 zinc finger transcription factors (TFs) that can regulate various aspects of vascular biology, but currently, the roles of KLF2 in mediating the adverse vascular effects of NMs have gained little attention by toxicologists. This review summarized current knowledge about the adverse vascular effects of NMs and proposed the potential roles of KLFs in mediating these effects based on available data from toxicological studies as well as the current understanding about KLFs in vascular biology. Finally, the challenges in investigating the role of KLFs in vascular toxicology were also summarized. Considering the important roles of KLFs in vascular biology, further studies are needed to understand the influence of NMs on KLFs and the downstream events.

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Endoplasmic reticulum stress-dependent oxidative stress mediated vascular injury induced by silica nanoparticles in vivo and in vitro

Cited by 30 publications

References 65 publications

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

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

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

Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

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