2. Academic Validation
  3. Antiferroptosis therapy alleviated the development of atherosclerosis

Antiferroptosis therapy alleviated the development of atherosclerosis

  • MedComm (2020). 2024 Apr 4;5(4):e520. doi: 10.1002/mco2.520.
Zhou Yang 1 2 3 4,  Yue He 5 6 7,  Dejun Wu 8,  Weihao Shi 9,  Ping Liu 5 10,  Jinyun Tan 9,  Rui Wang 11,  Bo Yu 1 2 3 9
Affiliations

Affiliations

  • 1 Department of Vascular Surgery Shanghai Pudong Hospital Fudan University Pudong Medical Center Shanghai China.
  • 2 Fudan Zhangjiang Institute, Fudan University Shanghai China.
  • 3 Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling Shanghai China.
  • 4 Department of Head and Neck Surgery Fudan University Shanghai Cancer Center Shanghai China.
  • 5 Shanghai University of Traditional Chinese Medicine Shanghai China.
  • 6 Department of Cardiology Shanghai Eighth People's Hospital Shanghai China.
  • 7 Shanghai Engineering Research Center of AI Technology for Cardiopulmonary Diseases Shanghai China.
  • 8 Department of General Surgery Shanghai Pudong Hospital Fudan University Pudong Medical Center Shanghai China.
  • 9 Department of Vascular Surgery Huashan Hospital Affiliated to Fudan University Shanghai China.
  • 10 Shanghai University of Traditional Chinese Medicine Department of Cardiology Longhua Hospital Shanghai China.
  • 11 Department of Cardiovascular Surgery Nanjing First Hospital Nanjing Medical University Nanjing China.
PMID: 38576455 DOI: 10.1002/mco2.520
Abstract

Ferroptosis has been confirmed to be associated with various diseases, but the relationship between Ferroptosis and atherosclerosis (AS) remains unclear. Our research detailly clarified the roles of Ferroptosis in three continuous and main pathological stages of AS respectively (injury of endothelial cells [ECs], adhesion of monocytes, and formation of foam cells). We confirmed that oxidized low-density lipoprotein (ox-LDL), the key factor in the pathogenesis of AS, strongly induced Ferroptosis in ECs. Inhibition of Ferroptosis repressed the adhesion of monocytes to ECs by inhibiting inflammation of ECs. Ferroptosis also participated in the formation of foam cells and lipids by regulating the Cholesterol efflux of macrophages. Further research confirmed that ox-LDL repressedthe activity of Glutathione Peroxidase 4 (GPX4), the classic lipid peroxide scavenger. Treatment of a high-fat diet significantly induced Ferroptosis in murine aortas and aortic sinuses, which was accompanied by AS lesions and hyperlipidemia. Treatment with Ferroptosis inhibitors significantly reduced Ferroptosis, hyperlipidemia, and AS lesion development. In conclusion, our research determined that ox-LDL induced Ferroptosis by repressing the activity of GPX4. Antiferroptosis treatment showed promising treatment effects in vivo. Ferroptosis-associated indexes also showed promising diagnostic potential in AS patients.

Keywords

atherosclerosis; endothelial cells; ferroptosis; glutathione peroxidase 4; oxidized low‐density lipoprotein.

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