title: Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation.
abstract: 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.
authors.affiliation: The Lipid Research Laboratory, Rappaport Faculty of Medicine and Research Institute, Technion, Haifa, 31096, Israel.|The Technion Center of Excellence in Exposure Science and Environmental Health (TCEEH), Technion, Haifa, 32000, Israel.
authors.forename: Lauren
authors.initials: L
authors.lastname: Petrick
authors.affiliation: The Lipid Research Laboratory, Rappaport Faculty of Medicine and Research Institute, Technion, Haifa, 31096, Israel.
authors.forename: Mira
authors.initials: M
authors.lastname: Rosenblat
authors.affiliation: The Lipid Research Laboratory, Rappaport Faculty of Medicine and Research Institute, Technion, Haifa, 31096, Israel.
authors.forename: Nicole
authors.initials: N
authors.lastname: Paland
authors.affiliation: The Lipid Research Laboratory, Rappaport Faculty of Medicine and Research Institute, Technion, Haifa, 31096, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Aviram
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000139:chemically induced*; D002460:Cell Line; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D012307:Risk Factors; D012822:Silicon Dioxide / Q000633:toxicity*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D014280:Triglycerides; D012822:Silicon Dioxide
keywords: ATGL; cholesterol; macrophages; reactive oxygen species; silicon dioxide nanoparticles; triglycerides