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Mechanisms of Disease: β-adrenergic receptors—alterations in signal transduction and pharmacogenomics in heart failure

Nature Clinical Practice Cardiovascular Medicine volume 2, pages 475–483 (2005)Cite this article

Abstract

β-adrenergic signaling is an important regulator of myocardial function. During the progression of heart failure (HF), a reproducible series of biochemical events occurs that affects β-adrenergic receptor (β-AR) signaling and cardiac function. Furthermore, there are pathophysiologic alterations in the expression and regulation of proteins that are regulated by β-ARs during HF. Analyses of these complex signaling pathways have led to a better understanding of HF mechanisms and the use of β-adrenergic antagonists, which have notably altered HF-related morbidity and mortality. Despite therapeutic advances that have affected β-AR signaling, HF remains a leading cause of hospitalization and a principal cause of death in industrialized nations. In this review, we summarize current insights into β-adrenergic signal-transduction pathways, the best-described β-AR polymorphisms, and therapies that target the β-AR pathway in HF.

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Figure 1: Schematic of β-adrenergic and calcium intracellular trafficking in myocytes, showing ion channels, contractile pathways and β-adrenergic signal transduction.
Figure 2: Schematic of the desensitization and intracellular trafficking of β-adrenergic receptors.

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Author information

Authors and Affiliations

  1. Director of Heart Failure and Cardiac Transplantation,

    David S Feldman, Cynthia A Carnes, William T Abraham & Michael R Bristow

  2. Professor of Pharmacy and Biophysics,

    David S Feldman, Cynthia A Carnes, William T Abraham & Michael R Bristow

  3. Director of Cardiovascular Medicine, at Ohio State University, Columbus, OH, USA

    David S Feldman, Cynthia A Carnes, William T Abraham & Michael R Bristow

  4. professor of Cardiovascular Medicine at the University of Colorado Health Science Center, Denver, CO, USA

    David S Feldman, Cynthia A Carnes, William T Abraham & Michael R Bristow

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  1. David S Feldman
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Correspondence to David S Feldman.

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Competing interests

David Feldman has worked as a consultant for GlaxoSmithKline, Medtronic, SCIOS and Abbott. Michael Bristow has acted as a consultant for Astra Zeneca, Guidant, Mylan, Paracor, CVRx, Inspiration Medical, Cardiac Dimensions and Novartis; as an equity officer or director for Myogen and ARCA Discovery; and has received research support from Astra Zeneca, Guidant, Myogen, ARCA and Mylan.

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Feldman, D., Carnes, C., Abraham, W. et al. Mechanisms of Disease: β-adrenergic receptors—alterations in signal transduction and pharmacogenomics in heart failure. Nat Rev Cardiol 2, 475–483 (2005). https://doi.org/10.1038/ncpcardio0309

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