Nrf2 Ameliorates Atrial Fibrosis During Antithrombotic Therapy for Atrial Fibrillation by Modulating CYP2C9 Activity.

IF 2.6 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Cardiovascular Pharmacology Pub Date : 2024-10-01 DOI:10.1097/FJC.0000000000001618

Liting Wu, Zhumeng Li, Lijuan Xu, Yingchao Fan, Delong Mao, Hanxiao Sun, Wenfang Zhuang

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引用次数: 0

Abstract

Abstract: Anticoagulant therapy can significantly reduce the incidence of stroke and peripheral embolism events in patients with atrial fibrillation (AF). Although warfarin is widely used as an anticoagulant drug, a wrong dose can lead to increased risks of bleeding or blood clots. The aim of this study was to assess whether nuclear factor-erythroid-2-related factor 2 (Nrf2) can improve the efficacy of warfarin through the regulation of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) using a rat model of AF. Results showed that AF significantly reduced Nrf2 in myocardial tissue of sham-operated rats. Furthermore, Nrf2 overexpression effectively reduced AF-induced atrial fibrosis by reducing collagen in the left atrium, inhibiting the expression of the fibrosis-related genes collagen I and transforming growth factor-β1 in rats with AF. Nrf2 overexpression can activate CYP2C9, decrease the serum concentration of warfarin, and decrease prothrombin time and international normalized ratio in AF rats. In this article, Nrf2 overexpression protects against fibrosis, increased survival in AF rats, and activated CYP2C9 expression, thus broadening the therapeutic range of warfarin in AF rats.

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Nrf2通过调节CYP2C9的活性改善心房颤动抗栓治疗期间的心房纤维化。

抗凝疗法可大大降低心房颤动（房颤）患者中风和外周栓塞事件的发生率。虽然华法林作为一种抗凝药物被广泛使用，但错误的剂量会导致出血或血栓风险增加。本研究旨在利用大鼠房颤模型评估核因子-红细胞-2相关因子2（Nrf2）是否能通过调节细胞色素P450家族2亚家族C成员9（CYP2C9）来改善华法林的疗效。结果表明，房颤会明显降低假手术大鼠心肌组织中的Nrf2。此外，Nrf2的过表达可减少左心房的胶原蛋白，抑制房颤大鼠纤维化相关基因胶原蛋白I和转化生长因子-β1的表达，从而有效减少房颤诱发的心房纤维化。Nrf2 的过表达能激活 CYP2C9，降低华法林的血清浓度，减少房颤大鼠的凝血酶原时间和国际标准化比率。在此，Nrf2过表达可防止房颤大鼠纤维化，提高其存活率，并激活CYP2C9的表达，从而扩大华法林对房颤大鼠的治疗范围。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cardiovascular Pharmacology 医学-心血管系统

CiteScore

5.10

自引率

3.30%

发文量

367

审稿时长

1 months

期刊介绍： Journal of Cardiovascular Pharmacology is a peer reviewed, multidisciplinary journal that publishes original articles and pertinent review articles on basic and clinical aspects of cardiovascular pharmacology. The Journal encourages submission in all aspects of cardiovascular pharmacology/medicine including, but not limited to: stroke, kidney disease, lipid disorders, diabetes, systemic and pulmonary hypertension, cancer angiogenesis, neural and hormonal control of the circulation, sepsis, neurodegenerative diseases with a vascular component, cardiac and vascular remodeling, heart failure, angina, anticoagulants/antiplatelet agents, drugs/agents that affect vascular smooth muscle, and arrhythmias. Appropriate subjects include new drug development and evaluation, physiological and pharmacological bases of drug action, metabolism, drug interactions and side effects, application of drugs to gain novel insights into physiology or pathological conditions, clinical results with new and established agents, and novel methods. The focus is on pharmacology in its broadest applications, incorporating not only traditional approaches, but new approaches to the development of pharmacological agents and the prevention and treatment of cardiovascular diseases. Please note that JCVP does not publish work based on biological extracts of mixed and uncertain chemical composition or unknown concentration.