线粒体NOX4通过氧化还原依赖结构改造和纤维化驱动心房动
Roberto Ramos Mondragon1, Aleksandr E Vendrov2, Andrey Lozhkin2
1Department of Pharmacology, University of Michigan, West Medical Center Dr., 230' Medical Science Research Building III, Ann Arbor, MI, 48109, USA.
Free radical biology & medicine
|November 3, 2025
概括
线粒体NOX4过度表达驱动心房动 (AF) 通过促进纤维重塑,而不是电变化. 准线粒体NOX4可能会预防AF和衰老的心脏病.
科学领域:
- 心血管生物学 心血管生物学
- 线粒体医学 线粒体医学
- 心脏电生理学 心脏电生理学
背景情况:
- 线粒体氧化应激会导致与年龄有关的心血管疾病和心律失常.
- 之前的研究将线粒体NOX4过度表达与心室节律失常联系在一起,但其在心房 (AF) 中的作用尚不清楚.
研究的目的:
- 调查线粒体NOX4在心房动 (AF) 的启动和维持中的作用.
- 阐明线粒体NOX4在心房重塑中的潜在心律失常机制.
主要方法:
- 使用了一个转基因小鼠模型 (Nox4TG) 具有针对线粒体的NOX4过度表达.
- 采用远程测量,心内记录,补丁电生理学,成像,组织学分析和高分辨率光学映射.
- 评估了心房组织的结构和功能变化.
主要成果:
- 与对照组相比,Nox4TG小鼠的自发性和节奏诱导的AF发作发生率较高.
- 尽管保留了动作潜力的持续时间和导电速度,但Nox4TG心房表现出显著的结构重塑,包括纤维化增加和重塑标记物的表达.
- 塞塔纳西布抑制NOX4减少了AF持续时间.
结论:
- 线粒体NOX4通过对氧化反应敏感的纤维细胞重塑促进AF,独立于对离子电流或处理的直接影响.
- 氧化应激具有室内特定的后果,突显了线粒体NOX4在心房重塑中的重要性.
- 准线粒体NOX4可能是一个治疗策略,以减轻心房重塑和老年心脏的AF.
相关概念视频
01:28Mechanism of Cardiac Arrhythmias
1.6K
Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
1.6K
01:43Electron Transport Chain: Complex III and IV
9.0K
During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
9.0K
01:45Mitochondrial Membranes
16.6K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
16.6K
01:46Electron Transport Chain: Complex I and II
18.4K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
18.4K
01:48ATP Synthase: Mechanism
16.7K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
16.7K
01:19Electrophysiology of Normal Cardiac Rhythm
8.7K
The normal cardiac rhythm is a synchronized electrical activity that facilitates the regular and coordinated contraction of the heart muscle. This process is essential for efficient blood circulation throughout the body. The fundamental elements involved in establishing and maintaining this rhythm include the unique electrical properties of cardiac muscle cells, the sinoatrial (SA) node's pacemaker function, the specialized conducting system, and the ionic mechanisms underlying each phase...
8.7K