Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
Blood. 2014 Jan 30;123(5):625-31. doi: 10.1182/blood-2013-09-512749. Epub 2013 Dec 3.
Despite the damaging effect on tissues at a high concentration, it has been gradually established that oxidative stress plays a positive role during angiogenesis. In adults, physiological or pathological angiogenesis is initiated by tissue demands for oxygen and nutrients, resulting in a hypoxia/reoxygenation cycle, which, in turn promotes the formation of reactive oxygen species (ROS). The ROS can be generated either endogenously, through mitochondrial electron transport chain reactions and nicotinamide adenine dinucleotide phosphate oxidase, or exogenously, resulting from exposure to environmental agents, such as ultraviolet or ionizing radiation. In many conditions, ROS promotes angiogenesis, either directly or via the generation of active oxidation products, including peroxidized lipids. The latter lipid metabolites are generated in excess during atherosclerosis, thereby linking atherogenic processes and pathological angiogenesis. Although the main mechanism of oxidative stress-induced angiogenesis involves hypoxia-inducible factor/vascular endothelial growth factor (VEGF) signaling, recent studies have identified several pathways that are VEGF-independent. This review aims to provide a summary of the past and present views on the role of oxidative stress as a mediator and modulator of angiogenesis, and to highlight newly identified mechanisms.
尽管高浓度的氧化应激对组织有破坏作用，但已逐渐证实氧化应激在血管生成中发挥积极作用。在成年人中，生理性或病理性血管生成是由组织对氧气和营养物质的需求引发的，导致缺氧/再氧合循环，进而促进活性氧（ROS）的形成。ROS 可以通过线粒体电子传递链反应和烟酰胺腺嘌呤二核苷酸磷酸氧化酶的内源性产生，也可以通过暴露于环境因素（如紫外线或电离辐射）的外源性产生。在许多情况下，ROS 通过生成活性氧化产物（包括过氧化脂质）来促进血管生成，直接或间接地促进血管生成。在动脉粥样硬化过程中，这些脂质代谢物过度生成，从而将动脉粥样硬化过程与病理性血管生成联系起来。尽管氧化应激诱导血管生成的主要机制涉及缺氧诱导因子/血管内皮生长因子（VEGF）信号通路，但最近的研究已经确定了几种与 VEGF 无关的途径。本文旨在总结过去和现在关于氧化应激作为血管生成的介质和调节剂的作用的观点，并强调新发现的机制。
