title: Magnetic ferroferric oxide nanoparticles induce vascular endothelial cell dysfunction and inflammation by disturbing autophagy.
abstract: Despite the considerable use of magnetic ferroferric oxide nanoparticles (Fe3O4NPs) worldwide, their safety is still an important topic of debate. In the present study, we detected the toxicity and biological behavior of bare-Fe3O4NPs (B-Fe3O4NPs) on human umbilical vascular endothelial cells (HUVECs). Our results showed that B-Fe3O4NPs did not induce cell death within 24h even at concentrations up to 400 μg/ml. The level of nitric oxide (NO) and the activity of endothelial NO synthase (eNOS) were decreased after exposure to B-Fe3O4NPs, whereas the levels of proinflammatory cytokines were elevated. Importantly, B-Fe3O4NPs increased the accumulation of autophagosomes and LC3-II in HUVECs through both autophagy induction and the blockade of autophagy flux. The levels of Beclin 1 and VPS34, but not phosphorylated mTOR, were increased in the B-Fe3O4NP-treated HUVECs. Suppression of autophagy induction or stimulation of autophagy flux, at least partially, attenuated the B-Fe3O4NP-induced HUVEC dysfunction. Additionally, enhanced autophagic activity might be linked to the B-Fe3O4NP-induced production of proinflammatory cytokines. Taken together, these results demonstrated that B-Fe3O4NPs disturb the process of autophagy in HUVECs, and eventually lead to endothelial dysfunction and inflammation.
authors.affiliation: College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001, China. Electronic address: chaperones@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001, China.
authors.forename: XueQin
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001, China.
authors.forename: YiMing
authors.initials: Y
authors.lastname: Miao
authors.affiliation: College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001, China.
authors.forename: ZhiQiang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001, China.
authors.forename: PengFei
authors.initials: P
authors.lastname: Qiang
authors.affiliation: College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001, China.
authors.forename: LiuQing
authors.initials: L
authors.lastname: Cui
authors.affiliation: College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Jing
authors.affiliation: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: YuQi
authors.initials: Y
authors.lastname: Guo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D058185:Magnetite Nanoparticles; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002097:C-Reactive Protein; D007770:L-Lactate Dehydrogenase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Autophagy dysfunction; Endothelial dysfunction; Inflammation; Magnetic ferroferric oxide nanoparticles