Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Feb 15, 2021; 12(2): 124-137
Published online Feb 15, 2021. doi: 10.4239/wjd.v12.i2.124
Role of ferroptosis in the process of diabetes-induced endothelial dysfunction
Er-Fei Luo, Hong-Xia Li, Yu-Han Qin, Yong Qiao, Gao-Liang Yan, Yu-Yu Yao, Lin-Qing Li, Jian-Tong Hou, Cheng-Chun Tang, Dong Wang
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 by National 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.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dong Wang, PhD, Doctor, Department of Cardiology, Zhongda Hospital, Southeast University, No. 87 Dingjiaqiao, Gulou District, Nanjing 210009, Jiangsu Province, China. wangdong_seu@163.com
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.