Bai JC, Yang HX, Zhan CC, Zhao LQ, Liu JR, Yang W. Hydrogen alleviates right ventricular hypertrophy by inhibiting ferroptosis via restoration of the Nrf2/HO-1 signaling pathway. World J Cardiol 2025; 17(6): 104832 [DOI: 10.4330/wjc.v17.i6.104832]
Corresponding Author of This Article
Wei Yang, MD, Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37 Yiyuan Street, Harbin 150000, Heilongjiang Province, China. weiyangyangwei@yeah.net
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jun-Cai Bai, Hong-Xiao Yang, Department of Cardiology, Zhengzhou University Affiliated Zhengzhou Central Hospital, Zhengzhou 450000, Henan Province, China
Jun-Cai Bai, Lu-Qi Zhao, Wei Yang, Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China
Cheng-Chuang Zhan, Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
Jia-Ren Liu, Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China
Co-first authors: Jun-Cai Bai and Hong-Xiao Yang.
Author contributions: Bai JC, Yang HX, and Zhan CC performed the experiments; Bai JC, Yang HX, and Zhan CC analyzed the data; Bai JC, Yang HX, Zhan CC, and Zhao LQ wrote the manuscript; Yang HX, Zhan CC, Zhao LQ, and Liu JR edited the manuscript; Liu JR and Yang HX critically revised the manuscript; Yang W designed the study and is the corresponding author. All the authors have read and approved the final manuscript. Bai JC and Yang HX contributed equally to this study.
Institutional review board statement: Institutional review board statement is not applicable to this study.
Institutional animal care and use committee statement: This study was approved by the Animal Care and Use Committee of the First Affiliated Hospital of Harbin Medical University.
Conflict-of-interest statement: The authors have nothing to disclose.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Data sharing statement: The data for this study can be obtained by contacting the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei Yang, MD, Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37 Yiyuan Street, Harbin 150000, Heilongjiang Province, China. weiyangyangwei@yeah.net
Received: January 8, 2025 Revised: February 26, 2025 Accepted: May 13, 2025 Published online: June 26, 2025 Processing time: 163 Days and 11.8 Hours
Abstract
BACKGROUND
Right ventricular hypertrophy (RVH) occurs because of volume or pressure overload within the right ventricular (RV) system. RVH is associated with complex pathological changes, including myocardial cell injury, apoptosis, myocardial fibrosis, neuroendocrine disturbances, and abnormal water and liquid metabolism. Ferroptosis, a novel type of iron-dependent cell death characterized by lipid peroxide accumulation, is an important mechanism of cardiomyocyte death. However, the role of ferroptosis in RVH has rarely been studied. We hypothesize that hydrogen (H2), an experimental medical gas with superior distribution characteristics, inhibits ferroptosis.
AIM
To explore the protective effect of H2 on RVH and the mechanism by which H2 regulates ferroptosis.
METHODS
An in vivo RVH rat model was induced by monocrotaline (MCT) in 30 male Sprague-Dawley rats. An H9C2 cell model was treated with angiotensin II to simulate pressure overload in the RV system in vitro. H2 was administered to rats by inhalation (2% for 3 hours daily for 21 days) and added to the cell culture medium. The Nrf2 inhibitor ML385 (1 μM) was used to investigate anti-ferroptotic mechanisms.
RESULTS
In MCT-treated rats, H2 inhalation decreased RVH; the RV wall thickness decreased from 3.5 ± 0.3 mm to 2.8 ± 0.2 mm (P < 0.05) and the RV ejection fraction increased from 45 ± 3% to 52 ± 4% (P < 0.05). In H9C2 cells, H2 alleviated hypertrophy. H2 inhibited ferroptosis by modulating the iron content, oxidative stress, and ferroptosis-related proteins, thereby restoring the Nrf2/HO-1 signaling pathway.
CONCLUSION
H2 retards RVH by inhibiting ferroptosis via Nrf2/HO-1 restoration, suggesting a new treatment strategy.
Core Tip: This study explored the protective effects of hydrogen (H2) on right ventricular hypertrophy (RVH) both in vivo and in vitro. The results revealed that H₂ inhibited ferroptosis, an iron-dependent cell death, by restoring the Nrf2/HO-1 pathway, offering new insights for treating RVH.
