From the Department of Pharmacology, Johannes Gutenberg University Medical Center, Mainz, Germany (U.F., N.X., H.L.); Center for Translational Vascular Biology (CTVB), Johannes Gutenberg University Medical Center, Mainz, Germany (H.L.); and German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany (H.L.).
Circ Res. 2017 Feb 17;120(4):713-735. doi: 10.1161/CIRCRESAHA.116.309326.
Major reactive oxygen species (ROS)-producing systems in vascular wall include NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase, xanthine oxidase, the mitochondrial electron transport chain, and uncoupled endothelial nitric oxide (NO) synthase. ROS at moderate concentrations have important signaling roles under physiological conditions. Excessive or sustained ROS production, however, when exceeding the available antioxidant defense systems, leads to oxidative stress. Animal studies have provided compelling evidence demonstrating the roles of vascular oxidative stress and NO in atherosclerosis. All established cardiovascular risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, and smoking enhance ROS generation and decrease endothelial NO production. Key molecular events in atherogenesis such as oxidative modification of lipoproteins and phospholipids, endothelial cell activation, and macrophage infiltration/activation are facilitated by vascular oxidative stress and inhibited by endothelial NO. Atherosclerosis develops preferentially in vascular regions with disturbed blood flow (arches, branches, and bifurcations). The fact that these sites are associated with enhanced oxidative stress and reduced endothelial NO production is a further indication for the roles of ROS and NO in atherosclerosis. Therefore, prevention of vascular oxidative stress and improvement of endothelial NO production represent reasonable therapeutic strategies in addition to the treatment of established risk factors (hypercholesterolemia, hypertension, and diabetes mellitus).
血管壁中主要的活性氧（ROS）产生系统包括 NADPH（烟酰胺腺嘌呤二核苷酸磷酸的还原形式）氧化酶、黄嘌呤氧化酶、线粒体电子传递链和无偶联的内皮一氧化氮（NO）合酶。在生理条件下，中等浓度的 ROS 具有重要的信号作用。然而，当产生的 ROS 超过可用的抗氧化防御系统时，就会导致氧化应激。动物研究提供了令人信服的证据，证明了血管氧化应激和 NO 在动脉粥样硬化中的作用。所有已确立的心血管危险因素，如高胆固醇血症、高血压、糖尿病和吸烟，都会增加 ROS 的产生并减少内皮细胞 NO 的产生。动脉粥样硬化形成的关键分子事件，如脂蛋白和磷脂的氧化修饰、内皮细胞激活和巨噬细胞浸润/激活，都受到血管氧化应激的促进和内皮细胞 NO 的抑制。动脉粥样硬化优先发生在血流紊乱的血管区域（拱部、分支和分叉处）。这些部位与增强的氧化应激和内皮细胞 NO 产生减少有关，这进一步表明 ROS 和 NO 在动脉粥样硬化中的作用。因此，除了治疗已确立的危险因素（高胆固醇血症、高血压和糖尿病）外，预防血管氧化应激和改善内皮细胞 NO 的产生代表了合理的治疗策略。
