title: [Simvastatin attenuates oxidized low density lipoprotein induced oxidative stress in human umbilical vein endothelial cells via downregulating NADPH oxidase activity].
abstract: OBJECTIVE
  To investigate the effects and related mechanism of simvastatin on oxidized low density lipoprotein(ox-LDL) induced oxidative stress in human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  HUVECs were cultured in 6 different culture media: control, ox-LDL, ox-LDL+vehicle, ox-LDL+0.1 µmol/L simvastatin, ox-LDL+0.5 µmol/L simvastatin, ox-LDL+1.0 µmol/L simvastatin. HUVECs were incubated with ox-LDL (120 µg/ml) for 24 h in the presence or absence of different concentrations of simvastatin (0.1,0.5, 1.0 µmol/L) . The fluorescence intensity for reactive oxygen species (ROS) in HUVECs was measured by a laser confocal scanning microscopy and a microplate reader.NADPH oxidase activity was measured by lucigenin chemiluminescence. p22(phox), gp91(phox), p47(phox) and p67(phox) mRNA expression of HUVECs post various treatments was detected by RT-PCR. p22(phox) immunoprecipitates were immunoblotted for p47(phox) and total p22(phox) levels to identify p47(phox)/p22(phox) interaction.
  
  
  RESULTS
  Simvastatin attenuated ox-LDL induced ROS generation and NADPH oxidase activity in a concentration dependent manner (all P < 0.05). In addition, simvastatin significantly downregulated mRNA expression of p22(phox), gp91(phox), p47(phox) and p67(phox) (all P < 0.05), as well as the interaction of p47(phox)/p22(phox) (P < 0.01).
  
  
  CONCLUSIONS
  Simvastatin is an important regulator on NADPH subunits mRNA expressions and p47(phox)/p22(phox) interaction. Simvastatin attenuates ox-LDL-induced oxidative stress in HUVECs via reducing NADPH oxidase activity.
authors.affiliation: Department of Clinical Pharmacy, Shimen County People's Hospital, Shimen 415300, China. Email: zhleishan@163.com.
authors.forename: Leishan
authors.initials: L
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Libao
authors.initials: L
authors.lastname: Cui
mesh_terms: D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000633:toxicity*; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D019821:Simvastatin; D019255:NADPH Oxidases