title: Novel aspects of ROS signalling in heart failure.
abstract: 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.
authors.affiliation: Division of Cardiovascular, King's College London British Heart Foundation Centre of Excellence, James Black Centre, 125 Coldharbour Lane, London, SE5 9NU, UK.
authors.forename: Anne D
authors.initials: AD
authors.lastname: Hafstad
authors.forename: Adam A
authors.initials: AA
authors.lastname: Nabeebaccus
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species