Division of Cardiovascular, King's College London British Heart Foundation Centre of Excellence, James Black Centre, 125 Coldharbour Lane, London, SE5 9NU, UK.
Basic Res Cardiol. 2013 Jul;108(4):359. doi: 10.1007/s00395-013-0359-8. Epub 2013 Jun 6.
Heart failure and many of the conditions that predispose to heart failure are associated with oxidative stress. This is considered to be important in the pathophysiology of the condition but clinical trials of antioxidant approaches to prevent cardiovascular morbidity and mortality have been unsuccessful. Part of the reason for this may be the failure to appreciate the complexity of the effects of reactive oxygen species. At one extreme, excessive oxidative stress damages membranes, proteins and DNA but lower levels of reactive oxygen species may exert much more subtle and specific regulatory effects (termed redox signalling), even on physiological signalling pathways. In this article, we review our current understanding of the roles of such redox signalling pathways in the pathophysiology of heart failure, including effects on cardiomyocyte hypertrophy signalling, excitation-contraction coupling, arrhythmia, cell viability and energetics. Reactive oxygen species generated by NADPH oxidase proteins appear to be especially important in redox signalling. The delineation of specific redox-sensitive pathways and mechanisms that contribute to different components of the failing heart phenotype may facilitate the development of newer targeted therapies as opposed to the failed general antioxidant approaches of the past.
心力衰竭和许多导致心力衰竭的病症都与氧化应激有关。这在该病症的病理生理学中被认为是很重要的，但抗氧化方法预防心血管发病率和死亡率的临床试验都没有成功。造成这种情况的部分原因可能是未能理解活性氧的影响的复杂性。在一个极端情况下，过度的氧化应激会破坏细胞膜、蛋白质和 DNA，但较低水平的活性氧可能会产生更微妙和特定的调节作用（称为氧化还原信号），甚至对生理信号通路也是如此。在本文中，我们回顾了我们目前对这些氧化还原信号通路在心力衰竭病理生理学中的作用的理解，包括对心肌细胞肥大信号、兴奋-收缩偶联、心律失常、细胞活力和能量代谢的影响。NADPH 氧化酶蛋白产生的活性氧似乎在氧化还原信号中特别重要。对导致心力衰竭表型不同成分的特定氧化还原敏感途径和机制的描绘，可能有助于开发新的靶向治疗方法，而不是过去失败的一般抗氧化方法。
