1 2nd Medical Clinic, Molecular Cardiology, Medical Center of the Johannes Gutenberg University , Mainz, Germany .
Antioxid Redox Signal. 2014 Jan 10;20(2):308-24. doi: 10.1089/ars.2012.4609. Epub 2012 Jul 13.
Oxidative stress is a well established hallmark of cardiovascular disease and there is strong evidence for a causal role of reactive oxygen and nitrogen species (RONS) therein.
Improvement of cardiovascular complications by genetic deletion of RONS producing enzymes and overexpression of RONS degrading enzymes proved the involvement of these species in cardiovascular disease at a molecular level. Vice versa, overexpression of RONS producing enzymes as well as deletion of antioxidant enzymes was demonstrated to aggravate cardiovascular complications.
With the present overview we present and discuss different pathways how mitochondrial RONS interact (crosstalk) with other sources of oxidative stress, namely NADPH oxidases, xanthine oxidase and an uncoupled nitric oxide synthase. The potential mechanisms of how this crosstalk proceeds are discussed in detail. Several examples from the literature are summarized (including hypoxia, angiotensin II mediated vascular dysfunction, cellular starvation, nitrate tolerance, aging, hyperglycemia, β-amyloid stress and others) and the underlying mechanisms are put together to a more general concept of redox-based activation of different sources of RONS via enzyme-specific "redox switches". Mitochondria play a key role in this concept providing redox triggers for oxidative damage in the cardiovascular system but also act as amplifiers to increase the burden of oxidative stress.
Based on these considerations, the characterization of the role of mitochondrial RONS formation in cardiac disease as well as inflammatory processes but also the role of mitochondria as potential therapeutic targets in these pathophysiological states should be addressed in more detail in the future.
氧化应激是心血管疾病的一个公认标志，有强有力的证据表明活性氧和氮物种（RONS）在其中起因果作用。
通过基因敲除 RONS 产生酶和过表达 RONS 降解酶来改善心血管并发症，证明了这些物质在心血管疾病中的分子水平上的参与。反之，过表达 RONS 产生酶以及删除抗氧化酶被证明会加重心血管并发症。
在本综述中，我们提出并讨论了不同的途径，即线粒体 RONS 如何与其他来源的氧化应激（如 NADPH 氧化酶、黄嘌呤氧化酶和非耦联的一氧化氮合酶）相互作用（串扰）。详细讨论了这种串扰的潜在机制。从文献中总结了几个例子（包括缺氧、血管紧张素 II 介导的血管功能障碍、细胞饥饿、硝酸盐耐受、衰老、高血糖、β-淀粉样蛋白应激等），并将潜在机制整合到一个更一般的概念中，即通过酶特异性的“氧化还原开关”，氧化还原激活不同来源的 RONS。线粒体在这一概念中起着关键作用，为心血管系统中的氧化损伤提供了氧化还原触发，但也作为放大器来增加氧化应激的负担。
基于这些考虑，未来应该更详细地研究线粒体 RONS 形成在心脏疾病以及炎症过程中的作用，以及线粒体作为这些病理生理状态下潜在治疗靶点的作用。
