Abstract: Objective Atherosclerotic lesions occur preferentially in the arterial branches, bifurcations and curvatures where
shear stress is low. We aimed to study the possible mechanisms involved in low shear stress (LSS)-induced oxidative damage
in vascular endothelial cells. Methods Human umbilical vein endothelial cells (HUVECs) exposed for 60 min to simulated LSS
using a parallel-plate flow chamber were examined for intracellular reactive oxygen species (ROS) and cell apoptosis with
chemiluminescence assay and TUNEL staining, respectively. Western blotting was used to determine the levels of endothelial
nitric oxide synthase (eNOS), P38, extracellular signal-regulate kinase (ERK) and c-Jun as well as their phosphorylation in cells
with LSS exposure for different time lengths. To investigate the signaling pathway involved in LSS-induced oxidative damage,
the cells were treated with P38, ERK and c-Jun inhibitors and examined for the expression of eNOS-Thr495 that negatively
regulated eNOS. Results Exposure to LSS for 1 h resulted in markedly increased ROS accumulation and apoptosis in HUVECs.
LSS exposure time-dependently enhanced the phosphorylation of eNOS, P38, ERK and c-Jun but did not significantly affect
their total protein expressions. Inhibition of ERK with PD98059 deactivated eNOS-Thr495 and restored super oxide dismutase
(SOD) activity, while inhibition of either p38 with SB202190 or c-Jun with SP600125 did no produce such effects. Conclusion
LSS-induced oxidative damage is partly due to activated mitogen-activated protein kinases (MAPK), among which ERK
contributes to decreased NO release in endothelial cells.