ORIGINAL RESEARCH article
Front. Physiol.
Sec. Clinical and Translational Physiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1516167
MAFF Mitigates Oxidative Stress and Pyroptosis in Cardiopulmonary Bypass-Induced Myocardium Injury
Provisionally accepted
Lei Yuan1
Duo Wang1Long Yuan2Dongdong Zheng1Cuilin Zhu1Hulin Piao1
MIxia LI1Yong Wang1
Zhicheng Zhu1Dan Li1Tiance Wang1
Kexiang Liu1*- 1Department of Cardiovascular Surgery, The Second Norman Bethune Hospital of Jilin University, Changchun, China
- 2Third Clinical Medical School, School of Acupuncture, Moxibustion and Tuina, Henan University of Chinese Medicine, Zhengzhou, Henan Province, China
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Background: Cardiopulmonary bypass (CPB) remains an indispensable technique for open-heart surgery; however, it induces systemic inflammation and oxidative stress, leading to myocardial cell damage and compromised prognosis. Optimizing myocardial protection during CPB remains a critical objective. This study aimed to identify potential therapeutic targets for myocardial protection during CPB. Methods: We performed weighted gene co-expression network analysis (WGCNA) on previously published datasets (GSE12486, GSE132176, GSE14956, and GSE38177) to identify CPB-related hub genes. An in vitro model of oxidative stress was established using H2O2-treated H9C2 cardiomyocytes to validate these hub genes. Through systematic validation, we identified the most representative hub gene. Subsequent functional studies, including gene knockdown and overexpression experiments, were conducted to elucidate its role and underlying mechanisms in oxidative stress-induced cardiomyocyte injury. Results: Integrated bioinformatics analysis and experimental validation identified MAFF as the most differentially expressed hub gene between pre- and post-CPB conditions. In the oxidative stress model, MAFF overexpression demonstrated cardioprotective effects by maintaining cell viability, significantly reducing reactive oxygen species (ROS) accumulation in both cytoplasm and mitochondria, and attenuating pyroptosis-mediated cell death. Conclusion: Our findings demonstrate that MAFF exerts protective effects against oxidative stress-induced cardiomyocyte injury, positioning it as a promising therapeutic target for myocardial protection. These results provide novel insights into optimizing postoperative recovery and improving clinical outcomes for patients undergoing CPB-assisted cardiac surgery.
Keywords: Cardiopulmonary Bypass, Myocardial injury, bioinformatics, MAFF, Reactive Oxygen Species, pyroptosis
Received: 23 Oct 2024; Accepted: 17 Jul 2025.
Copyright: © 2025 Yuan, Wang, Yuan, Zheng, Zhu, Piao, LI, Wang, Zhu, Li, Wang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kexiang Liu, Department of Cardiovascular Surgery, The Second Norman Bethune Hospital of Jilin University, Changchun, China
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