Yuan Lei, Wang Duo, Su Yale, Yuan Long, Li Mixia, Zheng Dongdong, Zhu Cuilin, Piao Hulin, Wang Yong, Zhu Zhicheng, Li Dan, Wang Tiance, Liu Kexiang
Department of Cardiovascular Surgery, The Second Norman Bethune Hospital of Jilin University, Changchun, Jilin, China.
Third Clinical Medical School, School of Acupuncture, Moxibustion and Tuina, Henan University of Chinese Medicine, Zhengzhou, Henan, China.
Front Physiol. 2025 Jul 31;16:1516167. doi: 10.3389/fphys.2025.1516167. eCollection 2025.
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.
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 model of oxidative stress was established using HO-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.
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.
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.
体外循环（CPB）仍然是心脏直视手术不可或缺的技术；然而，它会引发全身炎症和氧化应激，导致心肌细胞损伤并影响预后。在体外循环期间优化心肌保护仍然是一个关键目标。本研究旨在确定体外循环期间心肌保护的潜在治疗靶点。
我们对先前发表的数据集（GSE12486、GSE132176、GSE14956和GSE38177）进行加权基因共表达网络分析（WGCNA），以识别与体外循环相关的枢纽基因。使用过氧化氢处理的H9C2心肌细胞建立氧化应激模型来验证这些枢纽基因。通过系统验证，我们确定了最具代表性的枢纽基因。随后进行了包括基因敲低和过表达实验在内的功能研究，以阐明其在氧化应激诱导的心肌细胞损伤中的作用和潜在机制。
综合生物信息学分析和实验验证确定MAFF是体外循环前后条件下差异表达最明显的枢纽基因。在氧化应激模型中，MAFF过表达通过维持细胞活力、显著减少细胞质和线粒体中的活性氧（ROS）积累以及减轻焦亡介导的细胞死亡而表现出心脏保护作用。
我们的研究结果表明，MAFF对氧化应激诱导的心肌细胞损伤具有保护作用，使其成为心肌保护的一个有前景的治疗靶点。这些结果为优化接受体外循环辅助心脏手术患者的术后恢复和改善临床结局提供了新的见解。
