[Frontiers in Bioscience E4, 2131-2141, January 1, 2012]

Autophagy in the stress-induced myocardium

James McCormick1, Richard A Knight1, Sean P Barry2, Tiziano M Scarabelli3, Kadija Abounit3, David S Latchman4, Anastasis Stephanou1

1The Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, 2Department of Clinical Medicine, Trinity Centre for Health Sciences, St James's Hospital, Trinity College, Dublin, 3Centre for Heart and Vessel Preclinical Studies, St John Hospital Medical Centre, Wayne State University Medical School, Detroit, MI, USA, 4Birkbeck College, University of London, Malet Street, London, WC1E 7HX

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Free radical generation and cell death in the heart
3.1. Autophagic signalling
3.2. Gene disruption of mouse Atg5 leads to post partum lethality
3.3. The interplay between apoptosis and autophagy
3.4. Lysosome-associated membrane protein-2 (LAMP-2) deficiency causes vacuolar cardiomyopathy and myopathy
3.5. Autophagy: protector or destroyer of the cell?
3.6. Positive and negative regulators of autophagy
3.6.1. Signal transducer and activator of transcription 1
3.6.2. Signal transducer and activator of transcription 3
3.6.3. The tumour suppressors, p53 and p73, positively and negatively modulate autophagy
4. Concluding remarks
5. Acknowledgments
6. References

1. ABSTRACT

Cardiovascular disease is a leading cause of death worldwide, particularly in Western societies. During an ischaemic insult, ventricular pressure from the heart is diminished as a result of cardiac myocyte death by necrosis and apoptosis. Autophagy is a process whereby cells catabolise intracellular proteins in order to generate ATP in times of stress such as nutrient starvation and hypoxia. Emerging evidence suggests that autophagy plays a positive role in cardiac myocyte survival during periods of cellular stress performing an important damage limitation function. By promoting cell survival, cardiac myocyte loss is reduced thereby minimising the potential of heart failure. In contrast, it has been reported that autophagy can also be a form of cell death. By considering the various animal models of autophagy, we examine the role of the Signal Transducers and Activator of Transcription (STAT) proteins in the autophagic response. Additionally we review the role of the tumour suppressor, p53 and its family member p73 and their potential role in the autophagic response.