1. Academic Validation
  2. Nrf2-mediated redox balance alleviates LPS-induced vascular endothelial cell inflammation by inhibiting endothelial cell ferroptosis

Nrf2-mediated redox balance alleviates LPS-induced vascular endothelial cell inflammation by inhibiting endothelial cell ferroptosis

  • Sci Rep. 2024 Feb 9;14(1):3335. doi: 10.1038/s41598-024-53976-3.
Huimin Hou 1 2 Xiujiao Qin 1 Gaokai Li 3 Zhitao Cui 1 Jin Zhang 1 Bin Dong 1 Zhicheng Wang 4 Huiying Zhao 5
Affiliations

Affiliations

  • 1 Department of Geriatrics, First Hospital of Jilin University, Changchun, 130021, China.
  • 2 Department of Critical Care Medicine, Shandong First Medical University Affiliated Province Hospital, Jinan, 250023, China.
  • 3 School of Life and Health Science, Huzhou College, Huzhou, 313000, China.
  • 4 NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, 130021, China. zhicheng@jlu.edu.cn.
  • 5 Department of Geriatrics, First Hospital of Jilin University, Changchun, 130021, China. hui_ying@jlu.edu.cn.
Abstract

Ferroptosis plays an important role in inflammation and oxidative stress. Whether Ferroptosis is involved in the inflammation of vascular endothelial cells and its regulation mechanism remains unclear. We estimated the correlation between serum iron ion levels and the inflammation index of 33 patients with arteriosclerosis. In vitro, HUVECs with or without ferrostatin-1 were exposed to Lipopolysaccharide. Corresponding cell models to verify the target signaling pathway. The results showed that serum iron ion levels had a significant positive correlation with N ratio, N/L, LDL level, and LDL/HDL (P < 0.05), and a negative correlation with L ratio (P < 0.05) in the arteriosclerosis patients. In vitro, Ferroptosis is involved in HUVECs inflammation. Ferrostatin-1 can rescue LPS-induced HUVECs inflammation by decreasing HMGB1/IL-6/TNF-α expression. Nrf2 high expression could protect HUVECs against Ferroptosis by activating the GPX4/GSH system, inhibiting ferritinophagy, and alleviating inflammation in HUVECs by inhibiting HMGB1/IL-6/TNF-α expression. It also found that Nrf2 is a key adaptive regulatory factor in the oxidative damage of HUVECs induced by NOX4 activation. These findings indicated that Ferroptosis contributed to the pathogenesis of vascular endothelial cell damage by mediating endothelial cell inflammation. Nrf2-mediated redox balance in vascular inflammation may be a therapeutic strategy in vascular diseases.

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