2. Academic Validation
  3. Ferrostatin-1 suppresses cardiomyocyte ferroptosis after myocardial infarction by activating Nrf2 signaling

Ferrostatin-1 suppresses cardiomyocyte ferroptosis after myocardial infarction by activating Nrf2 signaling

  • J Pharm Pharmacol. 2023 Sep 20;rgad080. doi: 10.1093/jpp/rgad080.
Yu-Ting Wu 1 2,  Guo-Yong Zhang 2,  Yue Hua 2,  Hui-Jie Fan 3,  Xin Han 2,  Hong-Lin Xu 2,  Guang-Hong Chen 2,  Bin Liu 4,  Ling-Peng Xie 5,  Ying-Chun Zhou 2
Affiliations

Affiliations

  • 1 Binzhou Medical University Hospital, Binzhou 256603, China.
  • 2 School of Traditional Chinese Medicine, Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, Guangzhou 510515, China.
  • 3 Department of Traditional Chinese Medicine, Yangjiang People's Hospital, Yangjiang 529500, China.
  • 4 Guangzhou Institute of Cardiovascular Disease, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
  • 5 Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510000, China.
PMID: 37738327 DOI: 10.1093/jpp/rgad080
Abstract

Objectives: Ferroptosis, a new regulated cell death pathway, plays a crucial part in the development of Cardiovascular Disease. However, the precise underlying mechanism remains unclear. Therefore, this study aimed to elucidate this.

Methods: Herein, an erastin-induced H9C2 cell Ferroptosis in vitro model and a myocardial infarction murine model, which was created by ligating the left anterior descending coronary artery, were established. Ferroptosis-related indicators, myocardial injury-related indicators, and Nrf2 signaling-related proteins expression were analyzed to explore the potential mechanism underlying cardiomyocyte ferroptosis-mediated Cardiovascular Disease development.

Results: We demonstrated that Nrf2 downregulation in myocardial tissue, accompanied by ferroptotic events and changes in xCT and GPX4 expressions, induced cardiomyocyte Ferroptosis and myocardial injury after myocardial infarction. These events, including Ferroptosis and changes in Nrf2, xCT, and GPX4 expressions, were improved by ferrostatin-1 in vivo and in vitro. Besides, Nrf2 deficiency or inhibition aggravated myocardial infarction-induced cardiomyocyte Ferroptosis by decreasing xCT and GPX4 expressions in vivo and in vitro. Moreover, ferrostatin-1 directly targeted Nrf2, as evidenced by surface plasmon resonance analysis.

Conclusions: These results indicated that myocardial infarction is accompanied by cardiomyocyte Ferroptosis and that Nrf2 signaling plays a crucial part in regulating cardiomyocyte Ferroptosis after myocardial infarction.

Keywords

GPX4; Nrf2; ferroptosis; myocardial infarction; xCT.

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