Back to Journals » International Journal of Nanomedicine » Volume 9 » Issue 1

Silica nanoparticles induce autophagy and endothelial dysfunction via the PI3K/Akt/mTOR signaling pathway

Authors Duan J, Yu Y, Yu Y, Li Y, Wang J, Geng W, Jiang L, Li Q, Zhou X, Sun Z

Received 12 July 2014

Accepted for publication 12 September 2014

Published 5 November 2014 Volume 2014:9(1) Pages 5131—5141

DOI https://doi.org/10.2147/IJN.S71074

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang

Junchao Duan,1,2 Yongbo Yu,1,2 Yang Yu,1,2 Yang Li,1,2 Ji Wang,1,2 Weijia Geng,1,2 Lizhen Jiang,1,2 Qiuling Li,1,2 Xianqing Zhou,1,2 Zhiwei Sun1,2

1School of Public Health, Capital Medical University, Beijing, 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, People’s Republic of China

Abstract: Although nanoparticles have a great potential for biomedical applications, there is still a lack of a correlative safety evaluation on the cardiovascular system. This study is aimed to clarify the biological behavior and influence of silica nanoparticles (Nano-SiO2) on endothelial cell function. The results showed that the Nano-SiO2 were internalized into endothelial cells in a dose-dependent manner. Monodansylcadaverine staining, autophagic ultrastructural observation, and LC3-I/LC3-II conversion were employed to verify autophagy activation induced by Nano-SiO2, and the whole autophagic process was also observed in endothelial cells. In addition, the level of nitric oxide (NO), the activities of NO synthase (NOS) and endothelial (e)NOS were significantly decreased in a dose-dependent way, while the activity of inducible (i)NOS was markedly increased. The expression of C-reactive protein, as well as the production of proinflammatory cytokines (tumor necrosis factor α, interleukin [IL]-1β, and IL-6) were significantly elevated. Moreover, Nano-SiO2 had an inhibitory effect on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Our findings demonstrated that Nano-SiO2 could disturb the NO/NOS system, induce inflammatory response, activate autophagy, and eventually lead to endothelial dysfunction via the PI3K/Akt/mTOR pathway. This indicates that exposure to Nano-SiO2 is a potential risk factor for cardiovascular diseases.

Keywords: silica nanoparticles, endothelial dysfunction, autophagy, nitric oxide, inflammation

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Emerging and future therapies for hemophilia

Carr ME, Tortella BJ

Journal of Blood Medicine 2015, 6:245-255

Published Date: 3 September 2015

Patients’ acceptance of corticotomy-assisted orthodontics

Zawawi KH

Patient Preference and Adherence 2015, 9:1153-1158

Published Date: 12 August 2015

Acquired hemophilia A: emerging treatment options

Janbain M, Leissinger CA, Kruse-Jarres R

Journal of Blood Medicine 2015, 6:143-150

Published Date: 8 May 2015

Improving access to shared decision-making for Hispanics/Latinos with inadequately controlled type 2 diabetes mellitus

Davidson JA, Rosales A, Shillington AC, Bailey RA, Kabir C, Umpierrez GE

Patient Preference and Adherence 2015, 9:619-625

Published Date: 30 April 2015

Second case report of successful electroconvulsive therapy for a patient with schizophrenia and severe hemophilia A

Saito N, Shioda K, Nisijima K, Kobayashi T, Kato S

Neuropsychiatric Disease and Treatment 2014, 10:865-867

Published Date: 16 May 2014

The use of PEGylated liposomes in the development of drug delivery applications for the treatment of hemophilia

Rivka Yatuv, Micah Robinson, Inbal Dayan-Tarshish, et al

International Journal of Nanomedicine 2010, 5:581-591

Published Date: 6 August 2010

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010