[Frontiers in Bioscience E4, 1625-1637, January 1, 2012]

Beta-adrenoceptor signaling pathways mediate cardiac pathological remodeling

Yongnan Fu1, Han Xiao, Youyi Zhang1

1Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, PR China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Beta-adrenoceptor signaling pathways and cardiac hypertrophy
3.1. Gs/AC/cAMP/PKA signaling
3.2. MAPK signaling cascades
3.3. Ca2+/calcineurin/NFAT signaling
3.4. PI3K signaling cascades
3.5. Autocrine/paracrine
3.5.1. Renin-angiotensin system
3.5.2. IL-6 /STAT3 signaling pathway
3.6. Novel signaling pathways
3.6.1. Epac signaling pathway
3.6.2. Endocytosis signaling pathway
4. Beta-adrenoceptors and cardiac fibrosis
4.1. Beta2-adrenoceptors and cardiac fibroblast proliferation
4.2. Beta2-adrenoceptors and collagen synthesis
4.3. Beta-adrenoceptor stimulation induces cardiac fibrosis in vivo
4.4. Cell-cell communications in beta-adrenoceptor-mediated cardiac fibrosis
5. Beta-adrenoceptors and cardiomyocyte apoptosis
6. Conclusion
7. Acknowledgements
8. References

1. ABSTRACT

Beta-adrenoceptors (ARs), members of the G protein-coupled receptor (GPCR) superfamily, play a key role in the rapid regulation of myocardial function. Meanwhile, chronic catecholamine stimulation of adrenoceptors has been proved to be involved in the adverse myocardial remodeling, including cardiac hypertrophy, fibrosis, and apoptosis, which finally develop into heart failure. In the clinical situation, sympathetic hyperactivity is a key factor in the development of heart failure, and beta-blockers greatly improve the outcome of the disease. However, heart failure is still one of the leading causes of death. Therefore, a full understanding of the mechanism of beta-AR-mediated cardiac remodeling could indicate more targets for treating heart failure. This review summarizes a number of important signaling pathways involved in the process of cardiac pathological remodeling under chronic adrenergic stimulation.