title: Endothelial cell injury and dysfunction induced by silver nanoparticles through oxidative stress via IKK/NF-κB pathways.
abstract: Epidemiological studies have indicated that particulate matter (PM) exposure is most likely relevant to atherosclerosis. Endothelial cell injury and dysfunction are considered the early events in the initiation of atherosclerosis. Silver nanoparticles (AgNPs), with a smaller size and higher reactive activity, may induce much higher toxicity to endothelial cells compared with PM. However, few studies have been performed to determine the effect of AgNPs on endothelial cells. In the present study, human umbilical vein endothelial cells (HUVECs) were chosen as model cells to systematically explore the toxicity of AgNPs to endothelial cells. The obtained results indicated that exposure to AgNPs could inhibit proliferation, damage the cell membrane and seriously induce apoptosis. Simultaneously, the inflammatory cytokines, adhesion molecules, and chemokines of HUVECs were clearly up-regulated, which resulted in the adhesion of many monocytes to endothelial cells. More importantly, we found that dysfunctions of endothelial cells could be ascribed to the activation of NF-κB pathways. Furthermore, an oxidation inhibitor, N-acetyl-l-cysteine (NAC), effectively antagonized all of the AgNPs-induced responses, which indicated the key role of ROS production during the exposure of AgNPs in the toxicity of endothelial cells. In summary, our results clearly demonstrated that AgNPs could induce the injury and dysfunction of HUVECs through the activation of IKK/NF-κB, which is associated with oxidative stress, suggesting that exposure to AgNPs may be a potential hazardous factor for early atherosclerosis.
authors.affiliation: Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Junpeng
authors.initials: J
authors.lastname: Shi
authors.affiliation: Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zou
authors.affiliation: Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Du
authors.affiliation: Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China. Electronic address: hwzhang@iue.ac.cn.
authors.forename: Hongwu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012834:Silver / Q000633:toxicity*
chemical_list: C111835:CCL2 protein, human; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012834:Silver; D051550:I-kappa B Kinase
keywords: Atherosclerosis; Endothelium; NF-κB; Reactive oxygen species; Silver nanoparticles