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已发表论文
Nrf 家族及其心脏保护潜力：机制、功能与治疗前景
Authors Cui C , Song H, Guo Y, Shi J, Geng B, Wang G
Received 17 June 2025
Accepted for publication 26 August 2025
Published 15 September 2025 Volume 2025:19 Pages 8339—8373
DOI https://doi.org/10.2147/DDDT.S547848
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Anastasios Lymperopoulos
Chao Cui,1,* Hui Song,2,* Yifeng Guo,3 Jingfei Shi,4 Biao Geng,5 Gang Wang6
1Scientific Research Department, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, People’s Republic of China; 2Department of TCM, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, People’s Republic of China; 3Clinical Laboratory, Xintai Second People’s Hospital of Shandong, Taian, Shandong, People’s Republic of China; 4Department of Clinical and Basic Medicine, Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 5Department of Pharmacy, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China; 6Department of Cardiovascular Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Biao Geng; Gang Wang, Email gengbiao1988@163.com; wanggangtyfy@126.com
Abstract: This review systematically elucidates the molecular mechanisms and therapeutic potential of nuclear factor erythroid 2-related factor (Nrf) family members in the cardiovascular system. As critical components of the CNC-bZIP transcription factor family, the Nrf family (including Nrf-2/NFE2L2, Nrf-1/NFE2L1, and Nrf-3/NFE2L3) orchestrates antioxidant response element (ARE)-dependent gene expression networks, playing pivotal roles in maintaining redox homeostasis, modulating inflammatory responses, improving mitochondrial function, and regulating programmed cell death (apoptosis, autophagy, and pyroptosis). Clinical data have demonstrated that in patients with myocardial infarction, the expression of Nrf-3 gene is significantly upregulated in myocardial cells within the infarcted area. Its high expression is associated with increased in-hospital mortality during the acute phase and accelerated progression of ventricular remodeling. Knockout of the Nrf-3 gene can reduce the acute-phase mortality of myocardial infarction, improve ventricular remodeling, and enhance cardiac function. Additionally, a crossover trial involving 19 participants showed that after 2 months of administration of olive oil by-product pâté tablets, the plasma Nrf-2 level in the subjects increased by 88.9% with concurrent improvement in cardiovascular risk factors. Collectively, these findings confirm the impact of the Nrf family on cardiovascular prognosis and its potential for intervention. Furthermore, we comprehensively analyze the regulatory functions of Nrf members in major cardiovascular pathologies, including myocardial ischemia-reperfusion injury, atherosclerotic plaque formation/stabilization, and heart failure progression. Based on recent advances, we also discuss innovative therapeutic strategies targeting the Nrf pathway, encompassing pharmacological activators, gene/epigenetic therapies, combinatorial approaches, and lifestyle interventions, thereby providing a theoretical framework and novel perspectives for the precision medicine of cardiovascular diseases.
Keywords: Nrf family, cardioprotection, oxidative stress, inflammation, mitochondria, programmed cell death
1Scientific Research Department, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, People’s Republic of China; 2Department of TCM, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, People’s Republic of China; 3Clinical Laboratory, Xintai Second People’s Hospital of Shandong, Taian, Shandong, People’s Republic of China; 4Department of Clinical and Basic Medicine, Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 5Department of Pharmacy, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China; 6Department of Cardiovascular Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Biao Geng; Gang Wang, Email gengbiao1988@163.com; wanggangtyfy@126.com
Abstract: This review systematically elucidates the molecular mechanisms and therapeutic potential of nuclear factor erythroid 2-related factor (Nrf) family members in the cardiovascular system. As critical components of the CNC-bZIP transcription factor family, the Nrf family (including Nrf-2/NFE2L2, Nrf-1/NFE2L1, and Nrf-3/NFE2L3) orchestrates antioxidant response element (ARE)-dependent gene expression networks, playing pivotal roles in maintaining redox homeostasis, modulating inflammatory responses, improving mitochondrial function, and regulating programmed cell death (apoptosis, autophagy, and pyroptosis). Clinical data have demonstrated that in patients with myocardial infarction, the expression of Nrf-3 gene is significantly upregulated in myocardial cells within the infarcted area. Its high expression is associated with increased in-hospital mortality during the acute phase and accelerated progression of ventricular remodeling. Knockout of the Nrf-3 gene can reduce the acute-phase mortality of myocardial infarction, improve ventricular remodeling, and enhance cardiac function. Additionally, a crossover trial involving 19 participants showed that after 2 months of administration of olive oil by-product pâté tablets, the plasma Nrf-2 level in the subjects increased by 88.9% with concurrent improvement in cardiovascular risk factors. Collectively, these findings confirm the impact of the Nrf family on cardiovascular prognosis and its potential for intervention. Furthermore, we comprehensively analyze the regulatory functions of Nrf members in major cardiovascular pathologies, including myocardial ischemia-reperfusion injury, atherosclerotic plaque formation/stabilization, and heart failure progression. Based on recent advances, we also discuss innovative therapeutic strategies targeting the Nrf pathway, encompassing pharmacological activators, gene/epigenetic therapies, combinatorial approaches, and lifestyle interventions, thereby providing a theoretical framework and novel perspectives for the precision medicine of cardiovascular diseases.
Keywords: Nrf family, cardioprotection, oxidative stress, inflammation, mitochondria, programmed cell death