Abstract
Atherosclerosis constitutes a proverbial pathogenic mechanism for cardio-cerebrovascular disease that accounts for the most common cause of disability and morbidity for human health worldwide. Endothelial dysfunction and inflammation are the key contributors to the progression of atherosclerosis. Glutaredoxin 2 (GLRX2) is abundantly existed in various tissues and possesses a range of pleiotropic efficacy including anti-oxidative and anti-inflammatory responses. However, its role in atherosclerosis is still undefined. Here, down-regulation of GLRX2 was validated in lipopolysaccha (LPS)-induced vascular endothelial cells (HUVECs). Moreover, elevation of GLRX2 reversed the inhibition of cell viability in LPS-treated HUVECs and decreased LPS-induced increases in cell apoptosis and caspase-3 activity. Additionally, enhancement of GLRX2 expression antagonized oxidative stress in HUVECs under LPS exposure by inhibiting ROS, lactate dehydrogenase and malondialdehyde production and increased activity of anti-oxidative stress superoxide dismutase. Notably, GLRX2 abrogated LPS-evoked transcripts and releases of pro-inflammatory cytokine (TNF-α, IL-6, and IL-1β), chemokine MCP-1 and adhesion molecule ICAM-1 expression. Furthermore, the activation of Nrf2/HO-1 signaling was demonstrated in LPS-stimulated HUVECs. Importantly, blockage of the Nrf2 pathway counteracted the protective roles of GLRX2 in LPS-triggered endothelial cell injury, oxidative stress and inflammatory response. Thus, these data reveal that GLRX2 may alleviate the progression of atherosclerosis by regulating vascular endothelial dysfunction and inflammation via the activation of the Nrf2 signaling, supporting a promising therapeutic approach for atherosclerosis and its complications.
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YL: Data curation; Investigation; Methodology; Resources; Software; Supervision; Validation; Visualization; Writing—original draft. JG: Formal analysis; Software; Data curation, Validation, review & editing. QW: Data curation; Investigation; Methodology; Formal analysis; Resources; Software; Validation; Writing—review & editing. NW: Data curation; Methodology; Investigation; Formal analysis; Validation; Resources. LZ: Data curation; Software; Methodology; Formal analysis; Validation. ZW: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Software; Validation. All authors read and approved the final manuscript.
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Liu, Y., Gong, J., Wang, Q. et al. Activation of the Nrf2/HO-1 axis by glutaredoxin 2 overexpression antagonizes vascular endothelial cell oxidative injury and inflammation under LPS exposure. Cytotechnology 76, 167–178 (2024). https://doi.org/10.1007/s10616-023-00606-x
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DOI: https://doi.org/10.1007/s10616-023-00606-x