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Silica nanoparticles enhance autophagic activity, disturb endothelial cell homeostasis and impair angiogenesis
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  • 作者:Junchao Duan (1) (2)
    Yongbo Yu (1) (2)
    Yang Yu (1) (2)
    Yang Li (1) (2)
    Peili Huang (1) (2)
    Xianqing Zhou (1) (2)
    Shuangqing Peng (3)
    Zhiwei Sun (1) (2)

    1. School of Public Health
    ; Capital Medical University ; Beijing ; 100069 ; P.R. China
    2. Beijing Key Laboratory of Environmental Toxicology
    ; Capital Medical University ; Beijing ; 100069 ; P.R. China
    3. Institute of Disease Control and Prevention
    ; Academy of Military Medical Sciences ; Beijing ; 100071 ; P.R. China
  • 关键词:Silica nanoparticles ; Autophagy ; Endothelium ; Angiogensis ; VEGFR2 ; Crosstalk ; Nanotoxicology
  • 刊名:Particle and Fibre Toxicology
  • 出版年:2014
  • 出版时间:December 2014
  • 年:2014
  • 卷:11
  • 期:1
  • 全文大小:2,611 KB
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  • 刊物主题:Pharmacology/Toxicology; Pneumology/Respiratory System; Nanotechnology and Microengineering;
  • 出版者:BioMed Central
  • ISSN:1743-8977
文摘
Background Given that the effects of ultrafine fractions ( Methods and results Ultrastructural changes of autophagy were observed in both vascular endothelial cells and pericytes in the heart of ICR mice by TEM. Autophagic activity and impaired angiogenesis were further confirmed by the immunohistochemistry staining of LC3 and VEGFR2. In addition, the immunohistochemistry results showed that SiNPs had an inhibitory effect on ICAM-1 and VCAM-1, but no obvious effect on E-selectin in vivo. The disruption of F-actin cytoskeleton occurred as an initial event in SiNPs-treated endothelial cells. The depolarized mitochondria, autophagic vacuole accumulation, LC3-I/LC3-II conversion, and the down-regulation of cellular adhesion molecule expression were all involved in the disruption of endothelial cell homeostasis in vitro. Western blot analysis indicated that the VEGFR2/PI3K/Akt/mTOR and VEGFR2/MAPK/Erk1/2/mTOR signaling pathway was involved in the cardiovascular toxicity triggered by SiNPs. Moreover, there was a crosstalk between the VEGFR2-mediated autophagy signaling and angiogenesis signaling pathways. Conclusions In summary, the results demonstrate that SiNPs induce autophagic activity in endothelial cells and pericytes, subsequently disturb the endothelial cell homeostasis and impair angiogenesis. The VEGFR2-mediated autophagy pathway may play a critical role in maintaining endothelium and vascular homeostasis. Our findings may provide experimental evidence and explanation for cardiovascular diseases triggered by nano-sized particles.

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