Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation
Version of Record online: 28 NOV 2014
© 2014 Wiley Periodicals, Inc.
Volume 31, Issue 6, pages 713–723, June 2016
How to Cite
Petrick, L., Rosenblat, M., Paland, N. and Aviram, M. (2016), Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation. Environ. Toxicol., 31: 713–723. doi: 10.1002/tox.22084
- Issue online: 5 MAY 2016
- Version of Record online: 28 NOV 2014
- Manuscript Accepted: 9 NOV 2014
- Manuscript Revised: 7 NOV 2014
- Manuscript Received: 6 APR 2014
- Technion Rappaport Family Research Institute and the Clinical Research Institute at Rambam (CRIR)
- silicon dioxide nanoparticles;
- reactive oxygen species;
Nanoparticle research has focused on their toxicity in general, while increasing evidence points to additional specific adverse effects on atherosclerosis development. Arterial macrophage cholesterol and triglyceride (TG) accumulation and foam cell formation are the hallmark of early atherogenesis, leading to cardiovascular events. To investigate the in vitro atherogenic effects of silicon dioxide (SiO2), J774.1 cultured macrophages (murine cell line) were incubated with SiO2 nanoparticle (SP, d = 12 nm, 0–20 µg/mL), followed by cellular cytotoxicity, oxidative stress, TG and cholesterol metabolism analyses. A significant dose-dependent increase in oxidative stress (up to 164%), in cytotoxicity (up to 390% measured by lactate dehydrogenase (LDH) release), and in TG content (up to 63%) was observed in SiO2 exposed macrophages compared with control cells. A smaller increase in macrophage cholesterol mass (up to 22%) was noted. TG accumulation in macrophages was not due to a decrease in TG cell secretion or to an increased TG biosynthesis rate, but was the result of attenuated TG hydrolysis secondary to decreased lipase activity and both adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein expression (by 42 and 25%, respectively). Overall, SPs showed pro-atherogenic effects on macrophages as observed by cytotoxicity, increased oxidative stress and TG accumulation. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 713–723, 2016.