Role of phosphoinositide 3-kinases in regulating cardiac function
Lynette Pretorius1,2, Kate L. Owen1,3, Julie R. McMullen1
1
Baker IDI Heart and Diabetes Institute, Melbourne Victoria, 8008, Australia, 2Faculty of Medicine, Nursing, and Health Sciences, Department of Medicine (Alfred Hospital), Monash University, Victoria, 3181, Australia, 3Faculty of Medicine, Dentistry, and Health Sciences, Department of Biochemistry and Molecular Biology, University of Melbourne, Victoria, 3010, Australia
TABLE OF CONTENTS
- 1. Abstract
- 2. Introduction
- 3. Phosphoinositide 3-kinase (PI3K)
- 4. Role of PI3K signaling in the heart: evidence from in vitro and ex vivo studies
- 5. In vivo studies investigating PI3K signaling in the healthy heart
- 5.1. PI3K(p110alpha) mediates physiological cardiomyocyte hypertrophy
- 5.2. PI3K(p110gamma) negatively regulates cardiac contractility
- 6. PI3K signaling in the failing heart
- 6.1. PI3K(p110alpha) attenuates pathological cardiac hypertrophy and associated changes in gene expression
- 6.2. Class IA PI3Ks promote cell survival
- 6.3. PI3K(p110alpha) reduces cardiac fibrosis
- 6.4. The role of PI3K(p110gamma) in settings of pathological stress
- 7. Conclusion
- 8. Acknowledgements
- 9. References
1. ABSTRACT
Phosphoinositide 3-kinases (PI3Ks) are important signaling proteins in the heart. Class IA PI3Ks (p110a
, b
) are critical regulators of physiological heart growth and cell survival, and are generally considered to be beneficial for heart function. In contrast, activation of class IB PI3K(p110g
) is detrimental for heart function, reducing cardiac contractility. This may have implications for the treatment of heart disease and failure. In vitro, ex vivo and in vivo studies have contributed to our understanding of PI3K signaling in the heart. This review summarizes class I PI3K signaling in the regulation of cardiac function, with a particular focus on the role of different PI3K isoforms in settings of heart disease.
