Luo EF, Li HX, Qin YH, Qiao Y, Yan GL, Yao YY, Li LQ, Hou JT, Tang CC, Wang D. Role of ferroptosis in the process of diabetes-induced endothelial dysfunction. World J Diabetes 2021; 12(2): 124-137 [PMID: 33594332 DOI: 10.4239/wjd.v12.i2.124]
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Luo EF, Li HX, Qin YH, Qiao Y, Yan GL, Yao YY, Li LQ, Hou JT, Tang CC, Wang D. Role of ferroptosis in the process of diabetes-induced endothelial dysfunction. World J Diabetes 2021; 12(2): 124-137 [PMID: 33594332 DOI: 10.4239/wjd.v12.i2.124]
Er-Fei Luo, Hong-Xia Li, Yu-Han Qin, Lin-Qing Li, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
Yong Qiao, Gao-Liang Yan, Yu-Yu Yao, Jian-Tong Hou, Cheng-Chun Tang, Dong Wang, Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China
Author contributions: Luo EF, Li HX, Wang D and Tang CC conceived and designed the experiments; Luo EF, Li HX, Qin YH and Li LQ performed the experiments and data analyses and wrote the manuscript; Yan GL, Qiao Y and Hou JT contributed to the quality control of data and algorithms; Yao YY helped perform the data analysis and manuscript revision with constructive discussions; all authors read and approved the final manuscript. Luo EF and Li HX contributed equally to this work and should be considered co-first authors.
Supported byNational Natural Science Foundation of China, No. 81800244 and No. 81670237.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of Zhongda Hospital, Affiliated to Southeast University (Approval No. 2018ZDKYSB047), and followed the principles of the Declaration of Helsinki.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Southeast University (Protocol No. 20190304012).
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Received: June 28, 2020 Peer-review started: June 28, 2020 First decision: October 21, 2020 Revised: November 30, 2020 Accepted: December 11, 2020 Article in press: December 11, 2020 Published online: February 15, 2021 Processing time: 208 Days and 18.6 Hours
Core Tip
Core Tip: Endothelial dysfunction is a critical and initiating contributor to the pathogenesis of diabetic cardiovascular complications. Ferroptosis is characterized by the accumulation of iron-induced lipid reactive oxygen species and depletion of plasma membrane unsaturated fatty acids. Our findings demonstrated that ferroptosis is involved in endothelial dysfunction and the p53- xCT (the substrate-specific subunit of system Xc-)-glutathione axis activation plays a crucial role in endothelial cell ferroptosis and endothelial dysfunction. These results provide important insights as inhibiting activation of the p53-xCT-glutathione axis and ferroptosis could attenuate diabetes-induced endothelial dysfunction and may be a novel strategy for the treatment of vascular complications in diabetes mellitus.
