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Updated: Jan 22, 2026

Human Saphenous Vein Endothelial Cell Isolation and Exposure to Controlled Levels of Shear Stress and Stretch
Published on: April 21, 2023
Oscillatory Shear Stress Induces Oxidative Stress via TLR4 Activation in Endothelial Cells
Zhimei Wang1, Feng Wang1, Xiangquan Kong1
1Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Background:
Oscillatory shear stress (OSS) disrupts endothelial homeostasis and promotes oxidative stress, which can lead to atherosclerosis. In atherosclerotic lesions, Toll-like receptor 4 (TLR4) is highly expressed. However, the molecular mechanism by which TLR4 modulates oxidative changes and the cell signaling transudation upon OSS is yet to be determined.
Methods And Results:
Carotid artery constriction (CAC) surgery and a parallel-plate flow chamber were used to modulate shear stress. The results showed that OSS significantly increased the oxidative burden, and this was partly due to TLR4 activation. OSS activated NOX2 and had no significant influence to NOX1 or NOX4 in endothelial cells (ECs). OSS phosphorylated caveolin-1, promoted its binding with endothelial nitric oxide synthase (eNOS), and resulted in deactivation of eNOS. TLR4 inhibition restored levels of nitric oxide (NO) and superoxide dismutase (SOD) in OSS-exposed cells.
Conclusion:
TLR4 modulates OSS-induced oxidative stress by activating NOX2 and suppressing eNOS.
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