Wang Haibo, Hartnett M Elizabeth
The John A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT 84132, USA.
Antioxidants (Basel). 2017 Jun 3;6(2):40. doi: 10.3390/antiox6020040.
Angiogenesis is the formation of new blood vessels from preexisting ones and is implicated in physiologic vascular development, pathologic blood vessel growth, and vascular restoration. This is in contrast to vasculogenesis, which is de novo growth of vessels from vascular precursors, or from vascular repair that occurs when circulating endothelial progenitor cells home into an area and develop into blood vessels. The objective of this review is to discuss the isoform-specific role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in physiologic and pathologic angiogenesis and vascular repair, but will not specifically address vasculogenesis. As the major source of reactive oxygen species (ROS) in vascular endothelial cells (ECs), NOX has gained increasing attention in angiogenesis. Activation of NOX leads to events necessary for physiologic and pathologic angiogenesis, including EC migration, proliferation and tube formation. However, activation of different NOX isoforms has different effects in angiogenesis. Activation of NOX2 promotes pathologic angiogenesis and vascular inflammation, but may be beneficial in revascularization in the hindlimb ischemic model. In contrast, activation of NOX4 appears to promote physiologic angiogenesis mainly by protecting the vasculature during ischemia, hypoxia and inflammation and by restoring vascularization, except in models of oxygen-induced retinopathy and diabetes where NOX4 activation leads to pathologic angiogenesis.
血管生成是指从已有的血管形成新的血管，与生理血管发育、病理性血管生长及血管修复有关。这与血管发生不同，血管发生是指血管前体细胞从头生长形成血管，或者是循环中的内皮祖细胞归巢到某一区域并发育成血管时发生的血管修复。本综述的目的是讨论烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOX）的亚型特异性在生理和病理性血管生成及血管修复中的作用，但不具体涉及血管发生。作为血管内皮细胞（ECs）中活性氧（ROS）的主要来源，NOX在血管生成中受到越来越多关注。NOX的激活会引发生理和病理性血管生成所需的事件，包括内皮细胞迁移、增殖和管腔形成。然而，不同的NOX亚型激活在血管生成中有不同作用。NOX2的激活促进病理性血管生成和血管炎症，但在后肢缺血模型中对血管重建可能有益。相比之下，NOX4的激活似乎主要通过在缺血、缺氧和炎症期间保护脉管系统以及恢复血管化来促进生理性血管生成，但在氧诱导性视网膜病变和糖尿病模型中，NOX4激活会导致病理性血管生成。
