Oxidative and nitrosative stress in the maintenance of myocardial function

Yixuan Zhang, Carlo G. Tocchetti, Thomas Krieg, An L. Moens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Reactive oxygen species (ROS) are generated by several different cellular sources, and their accumulation within the myocardium is widely considered to cause harmful oxidative stress. On the other hand, their role as second messengers has gradually emerged. The equilibrium of the nitroso/redox balance between reactive nitrogen species and ROS is crucial for the health of cardionvocytes. This review provides a comprehensive overview of sources of oxidative stress in cardiac myocytes and describes the role of the nitroso/redox balance in cardiac pathophysiology. Although the exact mechanism of ROS production by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox's) is not completely understood, Nox2 and Nox4 have particularly important roles within the myocardium. Increasing evidence suggests that Nox2 produces superoxide and Nox4 generates only hydrogen peroxide. We also discuss the key role of nitric oxide synthases (NOSs) in the maintenance of the nitroso/redox balance: uncoupled endothelial NOS has been suggested to shift from nitric oxide to ROS production, contributing to increased oxidative stress within the myocardium. Furthermore, we highlight the importance of sequentially targeting and/or regulating the specific sources of oxidative and nitrosative stress to prevent and/or reverse myocardial dysfunction. Inhibition of NADPH oxidase-dependent ROS is considered to be a potential strategy for treatment of cardiomyopathy. Neither in vivo nor clinical data are available for NADPH oxidase inhibitors. Specifically targeting the mitochondria with the antioxidant MitoQ would be a very promising translation approach, because it could prevent mitochondrial permeability transition pore opening when ROS are produced during heart reperfusion. Enhancing NO signaling could also be a promising therapeutic approach against myocardial dysfunction.
Original languageEnglish
Pages (from-to)1531-1540
JournalFree Radical Biology and Medicine
Issue number8
Publication statusPublished - 15 Oct 2012


  • Oxidative stress
  • Nitrosative stress
  • Myocytes
  • Superoxide
  • Mitochondria
  • eNOS uncoupling
  • Xanthine oxidase/xanthine oxidoreductase
  • Free radicals


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