[Frontiers in Bioscience 17, 248-261, January 1, 2012]

Cell death and survival signalling in the cardiovascular system

Joanna Tucka1, Martin Bennett1, Trevor Littlewood1,2

1Division of Cardiovascular Medicine, University of Cambridge, Box 110, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK, 2Department of Biochemistry,University of Cambridge,80 Tennis Court Road,Cambridge CB2 1GA,UK

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. How does cell death occur?
2.1.1. Apoptosis
2.1.2. Autophagy
2.1.3. The other side(s) of death signalling
3. Where and when does cell death occur in the cardiovascular system?
3.1. Heart
3.2. Vasculature
4. Survival pathways
5. Extracellular survival signals
5.1. Vascular smooth muscle cells
5.2. Cardiomyocytes
5.3. Endothelial cells
6 Intracellular survival signalling pathways
6.1. The Akt/PKB pathway
6.2. Non-Akt dependent pathways
7. Conclusions
8. Acknowledgements
9. References

1. ABSTRACT

The loss of cells is an important factor in many diseases, including those of the cardiovascular system. Whereas apoptosis is an essential process in development and tissue homeostasis, its occurrence is often associated with various pathologies. Apoptosis of neurons that fail to make appropriate connections is essential for the selection of correct neural signalling in the developing embryo, but its appearance in adults is often associated with neurodegenerative disease. Similarly, in the cardiovascular system, remodeling of the mammalian outflow tract during the transition from a single to dual series circulation with four chambers is accompanied by a precise pattern of cell death, but apoptosis of cardiomyocytes contributes to ischemia-reperfusion injury in the heart. In many cases, it is unclear whether apoptosis represents a causative association or merely a consequence of the disease itself. There are many excellent reviews on cell death in the cardiovascular system (1-5); in this review we outline the critical signalling pathways that promote the survival of cardiovascular cells, and their relevance to both physiological cell death and disease.