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Article

Hydrogen Attenuates Chronic Intermittent Hypoxia-Induced Cardiac Hypertrophy by Regulating Iron Metabolism

by
Jixian Song
1,2,†,
Qi Chen
1,2,†,
Shan Xu
1,2,3,
Yujing Gou
1,2,
Yajing Guo
1,2,
Cuiling Jia
1,2,
Chenbing Zhao
1,2,
Zhi Zhang
1,2,
Boliang Li
1,2,
Yashuo Zhao
1,2,3,* and
Ensheng Ji
1,2,*
1
Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China
2
Department of Physiology, Institute of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China
3
The First Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang 050013, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Curr. Issues Mol. Biol. 2023, 45(12), 10193-10210; https://doi.org/10.3390/cimb45120636
Submission received: 8 November 2023 / Revised: 12 December 2023 / Accepted: 13 December 2023 / Published: 16 December 2023
(This article belongs to the Special Issue Iron Metabolism: From Molecular Mechanisms to Molecular Imaging)
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Abstract

The present study aimed to investigate the impact of hydrogen (H2) on chronic intermittent hypoxia (CIH)-induced cardiac hypertrophy in mice by modulating iron metabolism. C57BL/6N mice were randomly allocated into four groups: control (Con), CIH, CIH + H2, and H2. The mice were exposed to CIH (21–5% FiO2, 3 min/cycle, 8 h/d), and received inhalation of a hydrogen–oxygen mixture (2 h/d) for 5 weeks. Cardiac and mitochondrial function, levels of reactive oxygen species (ROS), and iron levels were evaluated. The H9C2 cell line was subjected to intermittent hypoxia (IH) and treated with H2. Firstly, we found H2 had a notable impact on cardiac hypertrophy, ameliorated pathological alterations and mitochondrial morphology induced by CIH (p < 0.05). Secondly, H2 exhibited a suppressive effect on oxidative injury by decreasing levels of inducible nitric oxide synthase (i-NOS) (p < 0.05) and 4-hydroxynonenal (4-HNE) (p < 0.01). Thirdly, H2 demonstrated a significant reduction in iron levels within myocardial cells through the upregulation of ferroportin 1 (FPN1) proteins (p < 0.01) and the downregulation of transferrin receptor 1 (TfR1), divalent metal transporter 1 with iron-responsive element (DMT1(+ire)), and ferritin light chain (FTL) mRNA or proteins (p < 0.05). Simultaneously, H2 exhibited the ability to decrease the levels of Fe2+ and ROS in H9C2 cells exposed to IH (p < 0.05). Moreover, H2 mediated the expression of hepcidin, hypoxia-inducible factor-1α (HIF-1α) (p < 0.01), and iron regulatory proteins (IRPs), which might be involved in the regulation of iron-related transporter proteins. These results suggested that H2 may be beneficial in preventing cardiac hypertrophy, a condition associated with reduced iron toxicity.
Keywords: obstructive sleep apnea; hydrogen; chronic intermittent hypoxia; cardiac hypertrophy; mitochondrial dysfunction; ferroportin 1; hepcidin obstructive sleep apnea; hydrogen; chronic intermittent hypoxia; cardiac hypertrophy; mitochondrial dysfunction; ferroportin 1; hepcidin

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MDPI and ACS Style

Song, J.; Chen, Q.; Xu, S.; Gou, Y.; Guo, Y.; Jia, C.; Zhao, C.; Zhang, Z.; Li, B.; Zhao, Y.; et al. Hydrogen Attenuates Chronic Intermittent Hypoxia-Induced Cardiac Hypertrophy by Regulating Iron Metabolism. Curr. Issues Mol. Biol. 2023, 45, 10193-10210. https://doi.org/10.3390/cimb45120636

AMA Style

Song J, Chen Q, Xu S, Gou Y, Guo Y, Jia C, Zhao C, Zhang Z, Li B, Zhao Y, et al. Hydrogen Attenuates Chronic Intermittent Hypoxia-Induced Cardiac Hypertrophy by Regulating Iron Metabolism. Current Issues in Molecular Biology. 2023; 45(12):10193-10210. https://doi.org/10.3390/cimb45120636

Chicago/Turabian Style

Song, Jixian, Qi Chen, Shan Xu, Yujing Gou, Yajing Guo, Cuiling Jia, Chenbing Zhao, Zhi Zhang, Boliang Li, Yashuo Zhao, and et al. 2023. "Hydrogen Attenuates Chronic Intermittent Hypoxia-Induced Cardiac Hypertrophy by Regulating Iron Metabolism" Current Issues in Molecular Biology 45, no. 12: 10193-10210. https://doi.org/10.3390/cimb45120636

APA Style

Song, J., Chen, Q., Xu, S., Gou, Y., Guo, Y., Jia, C., Zhao, C., Zhang, Z., Li, B., Zhao, Y., & Ji, E. (2023). Hydrogen Attenuates Chronic Intermittent Hypoxia-Induced Cardiac Hypertrophy by Regulating Iron Metabolism. Current Issues in Molecular Biology, 45(12), 10193-10210. https://doi.org/10.3390/cimb45120636

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