RESUMO
<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>
