Brown David I, Griendling Kathy K
From the Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA.
Circ Res. 2015 Jan 30;116(3):531-49. doi: 10.1161/CIRCRESAHA.116.303584.
Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species (ROS) in normal physiological signaling has been elucidated. Signaling pathways modulated by ROS are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here, we review the current literature on ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases, including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy, and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis, and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress.
长期以来，氧化应激一直被认为与心血管疾病有关，但最近，活性氧（ROS）在正常生理信号传导中的作用已得到阐明。由ROS调节的信号通路复杂且具有区室化，而我们才刚刚开始识别特定靶点的分子修饰。在这里，我们综述了当前关于心血管系统中ROS信号传导的文献，重点关注ROS在正常生理学中的作用以及信号通路失调如何导致心血管疾病，包括动脉粥样硬化、缺血再灌注损伤、心肌病和心力衰竭。特别是，我们考虑ROS如何调节与表型调节、迁移和粘附、收缩性、增殖和肥大、血管生成、内质网应激、细胞凋亡和衰老相关的信号通路。了解ROS的特定靶点可能会指导下一代ROS修饰疗法的开发，以降低与氧化应激相关的发病率和死亡率。
