AI Article Synopsis
- The study investigates the connection between obstructive sleep apnea (OSA) and increased risk of heart disease by examining how ferroptosis, a type of cell death linked to iron overload, impacts heart injury caused by intermittent hypoxia (IH).
- In experiments with human heart cells and mice, researchers found that IH reduced critical protective proteins (GPX4 and xCT) and caused heart damage associated with higher ferroptosis levels and endoplasmic reticulum stress (ERS).
- Treatment with ferroptosis inhibitors and N-acetylcysteine showed promise in reducing heart injury and ERS in mice exposed to IH, suggesting that targeting ferroptosis may help in managing myocardial damage related to OSA.
Article 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.
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| http://dx.doi.org/10.1007/s11325-022-02692-1 | DOI Listing |
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