Gray Stephen P, Shah Ajay M, Smyrnias Ioannis
School of Cardiovascular Medicine & Sciences, King's College London British Heart Foundation Centre, London, UK.
Vasc Biol. 2019 Jul 11;1(1):H59-H66. doi: 10.1530/VB-19-0014. eCollection 2019.
The heart relies on complex mechanisms that provide adequate myocardial oxygen supply in order to maintain its contractile function. At the cellular level, oxygen undergoes one electron reduction to superoxide through the action of different types of oxidases (e.g. xanthine oxidases, uncoupled nitric oxide synthases, NADPH oxidases or NOX). Locally generated oxygen-derived reactive species (ROS) are involved in various signaling pathways including cardiac adaptation to different types of physiological and pathophysiological stresses (e.g. hypoxia or overload). The specific effects of ROS and their regulation by oxidases are dependent on the amount of ROS generated and their specific subcellular localization. The NOX family of NADPH oxidases is a main source of ROS in the heart. Seven distinct Nox isoforms (NOX1-NOX5 and DUOX1 and 2) have been identified, of which NOX1, 2, 4 and 5 have been characterized in the cardiovascular system. For the purposes of this review, we will focus on the effects of NADPH oxidase 4 (NOX4) in the heart.
心脏依赖复杂机制来提供充足的心肌氧供应，以维持其收缩功能。在细胞水平上，氧通过不同类型氧化酶（如黄嘌呤氧化酶、未偶联的一氧化氮合酶、NADPH氧化酶或NOX）的作用进行单电子还原生成超氧化物。局部产生的氧衍生活性物质（ROS）参与各种信号通路，包括心脏对不同类型生理和病理生理应激（如缺氧或负荷过重）的适应性反应。ROS的特定作用及其受氧化酶的调节取决于所产生ROS的量及其特定的亚细胞定位。NADPH氧化酶的NOX家族是心脏中ROS的主要来源。已鉴定出七种不同的Nox亚型（NOX1 - NOX5以及DUOX1和2），其中NOX1、2、4和5已在心血管系统中得到表征。出于本综述的目的，我们将重点关注NADPH氧化酶4（NOX4）在心脏中的作用。
