2. Academic Validation
  3. The role of ferroptosis and endoplasmic reticulum stress in intermittent hypoxia-induced myocardial injury

The role of ferroptosis and endoplasmic reticulum stress in intermittent hypoxia-induced myocardial injury

  • Sleep Breath. 2022 Aug 11. doi: 10.1007/s11325-022-02692-1.
Jiefeng Huang  # 1,  Hansheng Xie  # 1,  Yisong Yang  # 1,  Lida Chen 2,  Ting Lin 1,  Biying Wang 1,  Qi-Chang Lin 3
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University; Fujian Provincial Sleep-Disordered Breathing Clinic Center; Institute of Respiratory Disease, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian Province, People's Republic of China, 350005.
  • 2 Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Xiangcheng, Zhangzhou, 363000, China.
  • 3 Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University; Fujian Provincial Sleep-Disordered Breathing Clinic Center; Institute of Respiratory Disease, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian Province, People's Republic of China, 350005. [email protected].
  • # Contributed equally.
PMID: 35951213 DOI: 10.1007/s11325-022-02692-1
Abstract

Purpose: Obstructive sleep apnea (OSA) is related to increased risk of Cardiovascular Disease. Ferroptosis is a form of programmed cell death characterized by iron overload and plays critical roles in myocardial injury. This study aimed to investigate the role of Ferroptosis in intermittent hypoxia (IH)-induced myocardial injury involving endoplasmic reticulum stress (ERS).

Methods: AC16 human cardiomyocytes were exposed to IH or normoxia conditions. Mice were randomly grouped as follows: normal control (NC), IH, ferrostatin-1 + IH (FIH), and N-acetylcysteine + IH (AIH). The mRNA levels of GPX4, xCT, FTH1, and FACL4 in AC16 cells were detected by qRT-PCR. The protein levels of GPX4, xCT, NOX4, ATF4, CHOP, Bcl-2, and Bax in myocardial tissue were detected by Western blot analysis.

Results: The mRNA expression levels of GPX4 and xCT in AC16 cells were significantly lower in IH group than that of NC group. In IH mice, myocardial tissues were injured accompanied by increased level of Ferroptosis and ERS. Inhibition of Ferroptosis and treatment of N-acetylcysteine reduced ERS and myocardial injury in mice exposed to IH. In addition, compared to ferrostatin-1, N-acetylcysteine exerted a greater effect in relieving IH-induced myocardial damage and ERS.

Conclusions: Ferroptosis was involved in IH-related myocardial injury accompanied by the activation of ERS. Inhibition of Ferroptosis and acetylcysteine treatment alleviated IH-related myocardial injury, which may be a potential target for therapeutic approaches to OSA-induced myocardial injury.

Keywords

Endoplasmic reticulum stress; Ferroptosis; Intermittent hypoxia; Myocardial injury; Oxidative stress.

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