Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in $ ApoE^{−/−} $ mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
|---|---|
| Enthalten in: |
Particle and fibre toxicology - 17(2020), 1 vom: 02. Okt. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ma, Ru [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| BKL: | |
|---|---|
| Themen: |
Atherosclerosis |
| Anmerkungen: |
© The Author(s) 2020 |
|---|
| doi: |
10.1186/s12989-020-00380-0 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
OLC2119784310 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | OLC2119784310 | ||
| 003 | DE-627 | ||
| 005 | 20240323145141.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230504s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12989-020-00380-0 |2 doi | |
| 035 | |a (DE-627)OLC2119784310 | ||
| 035 | |a (DE-He213)s12989-020-00380-0-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |q VZ |
| 084 | |a 44.12 |2 bkl | ||
| 084 | |a 44.39 |2 bkl | ||
| 100 | 1 | |a Ma, Ru |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in $ ApoE^{−/−} $ mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © The Author(s) 2020 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Silica nanoparticles | |
| 650 | 4 | |a Atherosclerosis | |
| 650 | 4 | |a Foam cell | |
| 650 | 4 | |a Endoplasmic reticulum stress | |
| 650 | 4 | |a CD36 | |
| 700 | 1 | |a Qi, Yi |4 aut | |
| 700 | 1 | |a Zhao, Xinying |4 aut | |
| 700 | 1 | |a Li, Xueyan |4 aut | |
| 700 | 1 | |a Sun, Xuejing |4 aut | |
| 700 | 1 | |a Niu, Piye |4 aut | |
| 700 | 1 | |a Li, Yanbo |4 aut | |
| 700 | 1 | |a Guo, Caixia |0 (orcid)0000-0002-5207-8059 |4 aut | |
| 700 | 1 | |a Chen, Rui |4 aut | |
| 700 | 1 | |a Sun, Zhiwei |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Particle and fibre toxicology |d BioMed Central, 2004 |g 17(2020), 1 vom: 02. Okt. |h Online-Ressource |w (DE-627)474928276 |w (DE-600)2170936-1 |w (DE-576)121930742 |x 1743-8977 |7 nnns |
| 773 | 1 | 8 | |g volume:17 |g year:2020 |g number:1 |g day:02 |g month:10 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1186/s12989-020-00380-0 |z kostenfrei |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a SSG-OPC-PHA | ||
| 912 | |a SSG-OPC-DE-84 | ||
| 912 | |a GBV_ILN_11 | ||
| 912 | |a GBV_ILN_20 | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_24 | ||
| 912 | |a GBV_ILN_31 | ||
| 912 | |a GBV_ILN_39 | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_60 | ||
| 912 | |a GBV_ILN_62 | ||
| 912 | |a GBV_ILN_63 | ||
| 912 | |a GBV_ILN_65 | ||
| 912 | |a GBV_ILN_69 | ||
| 912 | |a GBV_ILN_73 | ||
| 912 | |a GBV_ILN_74 | ||
| 912 | |a GBV_ILN_95 | ||
| 912 | |a GBV_ILN_105 | ||
| 912 | |a GBV_ILN_110 | ||
| 912 | |a GBV_ILN_151 | ||
| 912 | |a GBV_ILN_161 | ||
| 912 | |a GBV_ILN_170 | ||
| 912 | |a GBV_ILN_206 | ||
| 912 | |a GBV_ILN_213 | ||
| 912 | |a GBV_ILN_230 | ||
| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_2003 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_2027 | ||
| 912 | |a GBV_ILN_2147 | ||
| 912 | |a GBV_ILN_2148 | ||
| 912 | |a GBV_ILN_2446 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4322 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4367 | ||
| 912 | |a GBV_ILN_4700 | ||
| 936 | b | k | |a 44.12 |j Arbeitsmedizin |j betriebliches Gesundheitswesen |j Arbeitsmedizin |j betriebliches Gesundheitswesen |q VZ |
| 936 | b | k | |a 44.39 |j Toxikologie |j Toxikologie |q VZ |
| 951 | |a AR | ||
| 952 | |d 17 |j 2020 |e 1 |b 02 |c 10 | ||