β‐adrenergic receptor signalling and its functional consequences in the diseased heart
- 19 February 2016
- journal article
- review article
- Published by Wiley in European Journal of Clinical Investigation
- Vol. 46 (4), 362-374
- https://doi.org/10.1111/eci.12598
Abstract
To maintain the balance between the demand of the body and supply (cardiac output), cardiac performance is tightly regulated via the parasympathetic and sympathetic nervous systems. In heart failure, cardiac output (supply) is decreased due to pathologic remodelling of the heart. To meet the demands of the body, the sympathetic system is activated and catecholamines stimulate β-adrenergic receptors (β-ARs) to increase contractile performance and cardiac output. Although this is beneficial in the acute phase, chronic β-ARs stimulation initiates a cascade of alterations at the cellular level, resulting in a diminished contractile performance of the heart. This narrative review includes results from previously published systematic reviews and clinical and basic research publications obtained via PubMed up to May 2015. We discuss the alterations that occur during sustained β-AR stimulation in diseased myocardium and emphasize the consequences of β-AR overstimulation for cardiac function. In addition, current treatment options as well as future therapeutic strategies to treat patients with heart failure to normalize consequences of β-AR overstimulation are discussed. The heart is able to protect itself from chronic stimulation of the β-ARs via desensitization and reduced membrane availability of the β-ARs. However, ultimately this leads to an impaired downstream signalling and decreased protein kinase A (PKA)-mediated protein phosphorylation. β-blockers are widely used to prevent β-AR overstimulation and restore β-ARs in the failing hearts. However, novel and more specific therapeutic treatments are needed to improve treatment of HF in the future.Keywords
Funding Information
- Seventh Framework Programme (241577)
- ICIN Netherlands Heart Institute
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