Free Radicals in Medicine Core, Division of Clinical Pharmacology, Vanderbilt University Medical Center , Nashville, Tennessee.
Antioxid Redox Signal. 2013 Oct 1;19(10):1085-94. doi: 10.1089/ars.2012.4604. Epub 2012 May 21.
The role of reactive oxygen species (ROS) in angiotensin II (AngII) induced endothelial dysfunction, cardiovascular and renal remodeling, inflammation, and fibrosis has been well documented. The molecular mechanisms of AngII pathophysiological activity involve the stimulation of NADPH oxidases, which produce superoxide and hydrogen peroxide. AngII also increases the production of mitochondrial ROS, while the inhibition of AngII improves mitochondrial function; however, the specific molecular mechanisms of the stimulation of mitochondrial ROS is not clear.
Interestingly, the overexpression of mitochondrial thioredoxin 2 or mitochondrial superoxide dismutase attenuates AngII-induced hypertension, which demonstrates the importance of mitochondrial ROS in AngII-mediated cardiovascular diseases.
Although mitochondrial ROS plays an important role in normal physiological cell signaling, AngII, high glucose, high fat, or hypoxia may cause the overproduction of mitochondrial ROS, leading to the feed-forward redox stimulation of NADPH oxidases. This vicious cycle may contribute to the development of pathological conditions and facilitate organ damage in hypertension, atherosclerosis, and diabetes.
The development of antioxidant strategies specifically targeting mitochondria could be therapeutically beneficial in these disease conditions.
活性氧 (ROS) 在血管紧张素 II (AngII) 诱导的内皮功能障碍、心血管和肾脏重塑、炎症和纤维化中的作用已得到充分证实。AngII 病理生理活性的分子机制涉及 NADPH 氧化酶的刺激，该酶会产生超氧自由基和过氧化氢。AngII 还会增加线粒体 ROS 的产生，而抑制 AngII 则会改善线粒体功能；然而，刺激线粒体 ROS 的具体分子机制尚不清楚。
有趣的是，过表达线粒体硫氧还蛋白 2 或线粒体超氧化物歧化酶可减轻 AngII 诱导的高血压，这表明线粒体 ROS 在 AngII 介导的心血管疾病中很重要。
虽然线粒体 ROS 在正常生理细胞信号转导中发挥重要作用，但 AngII、高葡萄糖、高脂肪或低氧可能导致线粒体 ROS 的过度产生，从而导致 NADPH 氧化酶的正向还原刺激。这种恶性循环可能导致高血压、动脉粥样硬化和糖尿病等病理状况的发展，并促进器官损伤。
专门针对线粒体的抗氧化策略的开发可能对这些疾病状况具有治疗益处。
