[Frontiers in Bioscience 14, 3168-3187, January 1, 2009]

Redox sensitive signaling pathways in cardiac remodeling, hypertrophy and failure

Narayana Anilkumar, Alexander Sirker, Ajay M Shah

King's College London School of Medicine, The James Black Centre, Cardiovascular Division, London SE5 9NU, United Kingdom

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Reactive oxygen species as signaling molecules
4. Evidence for involvement of ROS in cardiac remodeling and failure
5. Sources of cellular ROS in heart failure
5.1. Mitochondrial ROS
5.2. Xanthine oxidase
5.3. NADPH oxidases
6. Redox signaling in cardiac hypertrophy 6.1 .Pro-hypertrophic effects of ROS and anti-hypertrophic effects of antioxidants 6.2 .GPCR-mediated cardiac hypertrophy 6.3 .Pressure overload and mechanical strain-induced hypertrophy 6.4 .Cardiac hypertrophy in response to other stimuli
7. Redox signaling in cardiac fibrosis and extracellular matrix remodeling 7.1. Clues from noncardiac settings to the importance of redox regulation in fibrosis
7.2. The role of NADPH oxidase-generated ROS in cardiac fibrosis 8. ROS in cardiac cell apoptosis
9. Reactive nitrogen species in myocardial hypertrophy and heart failure 10. Conclusions 11. Acknowledgements 12. References

1. ABSTRACT

Adaptation of the heart to intrinsic and external stress involves complex modifications at the molecular and cellular level that lead to tissue remodeling and functional compensation or failure depending upon the nature, intensity and chronicity of the stress. Signaling mechanisms mediated by reactive oxygen species (ROS) are now known to play important roles in many aspects of this complex process. In particular, the tightly regulated generation of ROS by NADPH oxidases appears especially important in key signaling events that drive the development of cardiomyocyte hypertrophy, fibrosis, extracellular matrix remodelling and cell apoptosis. This review discusses the signaling pathways modulated by ROS during the development of cardiac remodelling and failure with a particular emphasis on the role of NADPH oxidases.