title: Effects of atorvastatin on fine particle-induced inflammatory response, oxidative stress and endothelial function in human umbilical vein endothelial cells.
abstract: The study is to explore the toxicity of organic extracts and water-soluble fraction of fine particles on human umbilical vein endothelial cells (HUVECs). The exposure doses were 100, 200 and 400 μg/ml, respectively, for two kinds of fractions. Moreover, atorvastatin was used for intervention study. HUVECs were stimulated by 400 μg/ml organic and water soluble extracts, respectively, immediately followed by treatment with atorvastatin in concentrations of 0.1 μmol/L, 1 μmol/L and 10 μmol/L, respectively. Cell viability, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), reactive oxygen species (ROS) and the expression of interleukin-6 beta (IL-6), tumor necrosis factor-α (TNF-α), endothelin-1 and P-selectin were determined in cells. The results showed that MDA and ROS increased in HUVECs after exposed to organic extracts and water-soluble fraction, whereas cell viability, NO and SOD decreased. The mRNA expression of IL-6, TNF-α, endothelin-1 (ET-1) and P-selectin increased after exposed to different fractions. Meanwhile, at the same exposure dose, water-soluble fraction caused more significant increase of MDA, IL-6, TNF-α and P-selectin and decrease of cell viability and NO when compared to organic extracts. Compared to no atorvastatin group, the levels of MDA, ROS and the expression of IL-6, TNF-α, ET-1 and P-selectin decreased in HUVECs in adding atorvastatin group, but cell viability, NO and SOD increased, which indicated that atorvastatin attenuated fine particle-induced inflammatory response, oxidative stress and endothelial damage. The results hinted that the inflammatory response, oxidative stress and endothelial dysfunction might be the mechanisms of cardiovascular injury induced by different fractions of ambient fine particles.
authors.affiliation: Department of Environment Health, School of Public Health, Fudan University, The Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.
authors.forename: Jinzhuo
authors.initials: J
authors.lastname: Zhao
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Xie
authors.forename: Rongfang
authors.initials: R
authors.lastname: Jiang
authors.forename: Haidong
authors.initials: H
authors.lastname: Kan
authors.forename: Weimin
authors.initials: W
authors.lastname: Song
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular; D006538:Heptanoic Acids / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019007:P-Selectin / Q000378:metabolism; D052638:Particulate Matter / Q000633:toxicity*; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D000893:Anti-Inflammatory Agents; D019332:Endothelin-1; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D019007:P-Selectin; D052638:Particulate Matter; D011758:Pyrroles; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008315:Malondialdehyde; D000069059:Atorvastatin; D013482:Superoxide Dismutase