Peroxiredoxin 1 is Upregulated by Laminar Shear Stress via Nrf2 Transcription Factor

Endothelial cells (EC) exposed to oscillatory shear stress (OS) experience oxidative stress as a signature of atherosclerosis. Conversely, unidirectional laminar shear stress (LS) reduces reactive oxygen species (ROS) production and subsequent inflammatory responses. LS induces many protective genes via a shear‐sensitive antioxidant response element (ARE). We showed that the antioxidant enzyme peroxiredoxin 1 (PRX 1) is upregulated intracellularly by chronic LS, compared to OS and static (ST) culture. In addition, PRX 1‐knockdown attenuated LS‐dependent ROS reduction in EC. We hypothesize that shear‐dependent PRX 1 expression is regulated by ARE through the transcription factor nuclear factor (erythroid‐derived 2)‐related factor 2 (Nrf2). Quantitative, real‐time PCR indicated that chronic LS increased PRX 1 mRNA, compared to OS and ST. Immunoblots also showed increased PRX 1 protein expression in response to Nrf2 adenovirus infection of EC. These results indicate that shear‐dependent PRX 1 expression is regulated at the transcriptional level, and Nrf2 may play an important role in this mechanism. Through this pathway, PRX 1 acts as a mechanosensitive antioxidant implementing anti‐inflammatory and anti‐atherogenic effects of shear stress. Supported by NIH HL71014, HL75209, and HL70531 (HJ), Korean Ministry of Science & Technology FPR05C2‐510 (SWK), and AHA pre‐doctoral fellowship (ALM).