调节NOX2会导致肥胖引起的心房动
Arvind Sridhar1,2, Jaime DeSantiago1, Hanna Chen1
1Division of Cardiology.
The Journal of clinical investigation
|August 15, 2024
概括
肥胖会通过氧化应激增加心房动 (AF) 的风险. 抑制NADPH氧化酶2 (NOX2) 通过使离子通道和PITX2表达正常化,在肥胖小鼠和细胞中降低了AF.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 肥胖是心房动 (AF) 的重要危险因素,通常由增加的氧化压力介导.
- NADPH氧化酶2 (NOX2) 是心脏中反应性氧物种 (ROS) 的关键来源,与AF病原体有关,但其在与肥胖相关的AF中的确切作用尚未完全理解.
研究的目的:
- 调查NOX2介导的ROS产生的作用在肥胖引起的AF中.
- 阐明NOX2,氧化应激和肥胖中AF之间的分子机制.
主要方法:
- 使用了饮食诱导的肥胖 (DIO) 鼠标模型和人类诱导的多能干细胞衍生性心房心肌细胞 (hiPSC-aCMs).
- 给DIO小鼠使用NOX阻断剂 (apocynin) 和给PA治疗的hiPSC-aCMs使用NOX2特异性抑制剂.
- 进行了转录学分析,并使用过氧化作为NOX2替代物.
主要成果:
- NOX2抑制使心房动作潜力的持续时间正常化,并逆转与肥胖相关的离子通道重塑,减少AF负担.
- 转录组学揭示了NOX2上调配对类似的家庭主体转录因子2 (PITX2) 在肥胖中介的AF中.
- 增加的NOX2衍生的ROS与hiPSC-aCMs中PITX2表达升高直接相关.
结论:
- NOX2介导的ROS产生和随后的PITX2上调是与肥胖有关的心房重塑和AF的关键机制.
- 抑制NOX2是一种潜在的治疗策略,用于管理与肥胖相关的AF.
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