NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.
NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.
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DOI：
10.3390/antiox12101833
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发表时间：
2023-10-06
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影响因子：
--
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心房颤动（AF）是最常见的心律失常类型，其患病率随着年龄的增长而增加。心房的不规则和快速收缩可导致血液泵送无效，局部血瘀，血凝块，缺血性中风和心力衰竭。NADPH氧化酶（NOX）和线粒体是心脏活性氧的主要来源，NOX激活失调和线粒体功能障碍与房颤发病有关。NOX和线粒体来源的氧化应激通过诱导心房肌细胞的电生理变化和心房结构重塑，促进阵发性房颤的发生。由于高心房活动导致心肌细胞在持续性房颤期间消耗极高的能量来维持兴奋-收缩耦合，线粒体作为主要能量来源，承受代谢应激，影响其形态、Ca2+处理和ATP生成。在这篇综述中，我们讨论了氧化应激在激活AF触发的活性、调节细胞内Ca2+处理以及功能和解剖再入机制中的作用，所有这些都与AF的发生、延续和进展有关。细胞外基质、炎症、离子通道表达和功能、肌原纤维结构和线粒体功能的变化发生在房颤的早期过渡阶段，这为使用异型特异性NOX抑制剂和线粒体ROS清除剂以及改善线粒体动力学和代谢的药物靶向NOX和线粒体衍生的氧化应激打开了机会之窗，以治疗持续性房颤及其向永久性房颤过渡。
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and its prevalence increases with age. The irregular and rapid contraction of the atria can lead to ineffective blood pumping, local blood stasis, blood clots, ischemic stroke, and heart failure. NADPH oxidases (NOX) and mitochondria are the main sources of reactive oxygen species in the heart, and dysregulated activation of NOX and mitochondrial dysfunction are associated with AF pathogenesis. NOX- and mitochondria-derived oxidative stress contribute to the onset of paroxysmal AF by inducing electrophysiological changes in atrial myocytes and structural remodeling in the atria. Because high atrial activity causes cardiac myocytes to expend extremely high energy to maintain excitation-contraction coupling during persistent AF, mitochondria, the primary energy source, undergo metabolic stress, affecting their morphology, Ca2+ handling, and ATP generation. In this review, we discuss the role of oxidative stress in activating AF-triggered activities, regulating intracellular Ca2+ handling, and functional and anatomical reentry mechanisms, all of which are associated with AF initiation, perpetuation, and progression. Changes in the extracellular matrix, inflammation, ion channel expression and function, myofibril structure, and mitochondrial function occur during the early transitional stages of AF, opening a window of opportunity to target NOX and mitochondria-derived oxidative stress using isoform-specific NOX inhibitors and mitochondrial ROS scavengers, as well as drugs that improve mitochondrial dynamics and metabolism to treat persistent AF and its transition to permanent AF.
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