Birkenfeld, Andreas L. and Jordan, Jens and Dworak, Markus and Merkel, Tobias and Burnstock, Geoffrey (2018) Myocardial metabolism in heart failure: Purinergic signalling and other metabolic concepts. Pharmacology and Therapeutics, 194, pp. 132-144. Elsevier. doi: 10.1016/j.pharmthera.2018.08.015. ISSN 0163-7258.
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Abstract
Despite significant therapeutic advances in heart failure (HF) therapy, the morbidity and mortality associated with this disease remains unacceptably high. The concept of metabolic dysfunction as an important underlying mechanism in HF is well established. Cardiac function is inextricably linked to metabolism, with dysregulation of cardiac metabolism pathways implicated in a range of cardiac complications, including HF. Modulation of cardiac metabolism has therefore become an attractive clinical target. Cardiac metabolism is based on the integration of adenosine triphosphate (ATP) production and utilization pathways. ATP itself impacts the heart not only by providing energy, but also represents a central element in the purinergic signaling pathway, which has received considerable attention in recent years. Furthermore, novel drugs that have received interest in HF include angiotensin receptor blocker-neprilysin inhibitor (ARNi) and sodium glucose cotransporter 2 (SGLT-2) inhibitors, whose favorable cardiovascular profile has been at least partly attributed to their effects on metabolism. This review, describes the major metabolic pathways and concepts of the healthy heart (including fatty acid oxidation, glycolysis, Krebs cycle, Randle cycle, and purinergic signaling) and their dysregulation in the progression to HF (including ketone and amino acid metabolism). The cardiac implications of HF comorbidities, including metabolic syndrome, diabetes mellitus and cachexia are also discussed. Finally, the impact of current HF and diabetes therapies on cardiac metabolism pathways and the relevance of this knowledge for current clinical practice is discussed. Targeting cardiac metabolism may have utility for the future treatment of patients with HF, complementing current approaches.
Item URL in elib: | https://elib.dlr.de/124639/ | ||||||||||||||||||
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Document Type: | Article | ||||||||||||||||||
Title: | Myocardial metabolism in heart failure: Purinergic signalling and other metabolic concepts | ||||||||||||||||||
Authors: |
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Date: | 25 August 2018 | ||||||||||||||||||
Journal or Publication Title: | Pharmacology and Therapeutics | ||||||||||||||||||
Refereed publication: | Yes | ||||||||||||||||||
Open Access: | No | ||||||||||||||||||
Gold Open Access: | No | ||||||||||||||||||
In SCOPUS: | Yes | ||||||||||||||||||
In ISI Web of Science: | Yes | ||||||||||||||||||
Volume: | 194 | ||||||||||||||||||
DOI: | 10.1016/j.pharmthera.2018.08.015 | ||||||||||||||||||
Page Range: | pp. 132-144 | ||||||||||||||||||
Publisher: | Elsevier | ||||||||||||||||||
ISSN: | 0163-7258 | ||||||||||||||||||
Status: | Published | ||||||||||||||||||
Keywords: | Cardiac metabolism; Heart failure; Insulin resistance; Metabolic therapy; Purinergic signaling; | ||||||||||||||||||
HGF - Research field: | Aeronautics, Space and Transport | ||||||||||||||||||
HGF - Program: | Space | ||||||||||||||||||
HGF - Program Themes: | Research under Space Conditions | ||||||||||||||||||
DLR - Research area: | Raumfahrt | ||||||||||||||||||
DLR - Program: | R FR - Research under Space Conditions | ||||||||||||||||||
DLR - Research theme (Project): | R - Vorhaben Systemphysiologie (old) | ||||||||||||||||||
Location: | Köln-Porz | ||||||||||||||||||
Institutes and Institutions: | Institute of Aerospace Medicine > Muscle and Bone Metabolism | ||||||||||||||||||
Deposited By: | Becker, Christine | ||||||||||||||||||
Deposited On: | 11 Dec 2018 12:08 | ||||||||||||||||||
Last Modified: | 01 Oct 2020 12:40 |
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