Fang Qin, Bai Yang, Hu Shuiqing, Ding Jie, Liu Lei, Dai Meiyan, Qiu Jie, Wu Lujin, Rao Xiaoquan, Wang Yan
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Wuhan 430030, China.
Antioxidants (Basel). 2023 Nov 7;12(11):1978. doi: 10.3390/antiox12111978.
Pulmonary vascular remodeling, characterized by the thickening of all three layers of the blood vessel wall, plays a central role in the pathogenesis of pulmonary hypertension (PH). Despite the approval of several drugs for PH treatment, their long-term therapeutic effect remains unsatisfactory, as they mainly focus on vasodilation rather than addressing vascular remodeling. Therefore, there is an urgent need for novel therapeutic targets in the treatment of PH. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a vital transcription factor that regulates endogenous antioxidant defense and emerges as a novel regulator of pulmonary vascular remodeling. Growing evidence has suggested an involvement of Nrf2 and its downstream transcriptional target in the process of pulmonary vascular remodeling. Pharmacologically targeting Nrf2 has demonstrated beneficial effects in various diseases, and several Nrf2 inducers are currently undergoing clinical trials. However, the exact potential and mechanism of Nrf2 as a therapeutic target in PH remain unknown. Thus, this review article aims to comprehensively explore the role and mechanism of Nrf2 in pulmonary vascular remodeling associated with PH. Additionally, we provide a summary of Nrf2 inducers that have shown therapeutic potential in addressing the underlying vascular remodeling processes in PH. Although Nrf2-related therapies hold great promise, further research is necessary before their clinical implementation can be fully realized.
肺血管重塑以血管壁三层均增厚为特征,在肺动脉高压(PH)的发病机制中起核心作用。尽管已有几种治疗PH的药物获批,但它们的长期治疗效果仍不尽人意,因为这些药物主要侧重于血管舒张,而非解决血管重塑问题。因此,治疗PH迫切需要新的治疗靶点。核因子红细胞2相关因子2(Nrf2)是一种重要的转录因子,可调节内源性抗氧化防御,并且已成为肺血管重塑的新型调节因子。越来越多的证据表明Nrf2及其下游转录靶点参与了肺血管重塑过程。从药理学角度靶向Nrf2已在多种疾病中显示出有益效果,目前有几种Nrf2诱导剂正在进行临床试验。然而,Nrf2作为PH治疗靶点的确切潜力和机制仍不清楚。因此,这篇综述文章旨在全面探讨Nrf2在与PH相关的肺血管重塑中的作用和机制。此外,我们总结了在解决PH潜在血管重塑过程中显示出治疗潜力的Nrf2诱导剂。尽管与Nrf2相关的疗法前景广阔,但在其临床应用完全实现之前,仍需要进一步研究。
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