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Caixia Guo
Capital Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5207-8059
License:
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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 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.
Keywords
Silica nanoparticles, atherosclerosis, foam cell, endoplasmic reticulum stress, CD36
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CURRENT STATUS: Published
View the published article at Particle and Fibre Toxicology.
No community comments so far
Editorial decision: Accept
On 11 Sep, 2020
Editor assigned
On 08 Sep, 2020
Submission checks complete
On 07 Sep, 2020
Editor invited
On 07 Sep, 2020
Version 2
Posted 02 Jul, 2020
No comments provided
Editorial decision: Minor Revision
On 24 Aug, 2020
Review #3 received
Received 06 Jul, 2020
Reviewer #3 agreed
On 03 Jul, 2020
Review #2 received
Received 01 Jul, 2020
Review #1 received
Received 01 Jul, 2020
Editor assigned
On 30 Jun, 2020
Reviewers invited
Invitations sent on 30 Jun, 2020
Reviewer #1 agreed
On 30 Jun, 2020
Reviewer #2 agreed
On 30 Jun, 2020
Submission checks complete
On 29 Jun, 2020
Editor invited
On 29 Jun, 2020
No comments provided
Editorial decision: Major Revision
On 27 May, 2020
Review #3 received
Received 23 May, 2020
Review #1 received
Received 23 May, 2020
Review #2 received
Received 23 May, 2020
Reviewer #3 agreed
On 14 May, 2020
Reviewers invited
Invitations sent on 13 May, 2020
Reviewer #1 agreed
On 13 May, 2020
Reviewer #2 agreed
On 13 May, 2020
Editor assigned
On 07 May, 2020
Submission checks complete
On 06 May, 2020
Editor invited
On 06 May, 2020
First submitted
On 05 May, 2020
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Subject Areas
Toxicology
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A new preprint design is coming!
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See the published version of this preprint at Particle and Fibre Toxicology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Caixia Guo
Capital Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5207-8059
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Particle and Fibre Toxicology.
No community comments so far
Editorial decision: Accept
On 11 Sep, 2020
Editor assigned
On 08 Sep, 2020
Submission checks complete
On 07 Sep, 2020
Editor invited
On 07 Sep, 2020
Version 2
Posted 02 Jul, 2020
No comments provided
Editorial decision: Minor Revision
On 24 Aug, 2020
Review #3 received
Received 06 Jul, 2020
Reviewer #3 agreed
On 03 Jul, 2020
Review #2 received
Received 01 Jul, 2020
Review #1 received
Received 01 Jul, 2020
Editor assigned
On 30 Jun, 2020
Reviewers invited
Invitations sent on 30 Jun, 2020
Reviewer #1 agreed
On 30 Jun, 2020
Reviewer #2 agreed
On 30 Jun, 2020
Submission checks complete
On 29 Jun, 2020
Editor invited
On 29 Jun, 2020
No comments provided
Editorial decision: Major Revision
On 27 May, 2020
Review #3 received
Received 23 May, 2020
Review #1 received
Received 23 May, 2020
Review #2 received
Received 23 May, 2020
Reviewer #3 agreed
On 14 May, 2020
Reviewers invited
Invitations sent on 13 May, 2020
Reviewer #1 agreed
On 13 May, 2020
Reviewer #2 agreed
On 13 May, 2020
Editor assigned
On 07 May, 2020
Submission checks complete
On 06 May, 2020
Editor invited
On 06 May, 2020
First submitted
On 05 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Toxicology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Particle and Fibre Toxicology.
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
This is a list of supplementary files associated with this preprint. Click to download.
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