Role of ferroptosis in the process of diabetes-induced endothelial dysfunction

• DOI: 10.4239/wjd.v12.i2.124
• Publication Date: 2021-01-23T03:53:17Z
• Authors: 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
• Keywords: Endothelial Dysfunction

Background Endothelial dysfunction, a hallmark of diabetes, is critical and initiating contributor to the pathogenesis diabetic cardiovascular complications. However, underlying mechanisms are still not fully understood. Ferroptosis newly defined regulated cell death driven by cellular metabolism iron-dependent lipid peroxidation. Although involvement ferroptosis in disease has been shown cancers degenerative diseases, participation endothelial dysfunction remains unclear. Aim To examine role diabetes-induced mechanisms. Methods Human umbilical vein cells (HUVECs) were treated with high glucose (HG), interleukin-1β (IL-1β), inhibitor, then viability, reactive oxygen species (ROS), ferroptosis-related marker protein tested. further determine whether p53-xCT (the substrate-specific subunit system Xc-)-glutathione (GSH) axis involved HG IL-1β induced ferroptosis, HUVECs transiently transfected p53 small interfering ribonucleic acid or NC IL-1β. Cell ROS, assessed. In addition, we detected xCT expression aorta db/db mice. Results It was found that HUVECs, as evidenced protective effect inhibitors, Deferoxamine ferrostatin-1, resulting increased ROS decreased viability. Mechanistically, activation p53-xCT-GSH enhanced HUVECs. decrease presence de-endothelialized areas observed aortic endothelium Conclusion plays crucial dysfunction.