The mechanisms of ferroptosis and its role in atherosclerosis
- Biomed Pharmacother. 2024 Feb:171:116112. doi: 10.1016/j.biopha.2023.116112.
- 1. College of Nursing, Anhui University of Chinese Medicine, Hefei 230012, Anhui, PR China.
- 2. Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China.
- 3. Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China.
- 4. The First Clinical College, Guangdong Medical University, Zhanjiang 524000, Guangdong, PR China.
- 5. Division of Hepatobiliary and Pancreas Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou 570100, Hainan, PR China.
- 6. Emergency and Trauma College, Hainan Medical University, Haikou 570100, Hainan, PR China.
- 7. College of Nursing, Anhui University of Chinese Medicine, Hefei 230012, Anhui, PR China; Anhui Province Key Laboratory of Research & Development of Chinese Medicine, Hefei 230012, PR China. Electronic address: [email protected].
- 8. College of Nursing, Anhui University of Chinese Medicine, Hefei 230012, Anhui, PR China; Institute of Clinical Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou 570100, Hainan, PR China. Electronic address: [email protected].
Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS) and peroxidation of membrane polyunsaturated fatty acid Phospholipids (PUFA-PLs). Ferroptosis is unique among other cell death modalities in many aspects. It is initiated by excessive oxidative damage due to iron overload and lipid peroxidation and compromised antioxidant defense systems, including the system Xc-/ glutathione (GSH)/Glutathione Peroxidase 4 (GPX4) pathway and the GPX4-independent pathways. In the past ten years, Ferroptosis was reported to play a critical role in the pathogenesis of various cardiovascular diseases, e.g., Atherosclerosis (AS), arrhythmia, Heart Failure, diabetic Cardiomyopathy, and myocardial Ischemia-Reperfusion Injury. Studies have identified dysfunctional iron metabolism and abnormal expression profiles of ferroptosis-related factors, including iron, GSH, GPX4, Ferroportin (FPN), and SLC7A11 (xCT), as critical Indicators for atherogenesis. Moreover, Ferroptosis in plaque cells, i.e., vascular endothelial cell (VEC), macrophage, and vascular smooth muscle cell (VSMC), positively correlate with atherosclerotic plaque development. Many macromolecules, drugs, Chinese herbs, and food extracts can inhibit the atherogenic process by suppressing the Ferroptosis of plaque cells. In contrast, some Ferroptosis inducers have significant pro-atherogenic effects. However, the mechanisms through which Ferroptosis affects the progression of AS still need to be well-known. This review summarizes the molecular mechanisms of Ferroptosis and their emerging role in AS, aimed at providing novel, promising druggable targets for anti-AS therapy.