Birkenfeld, AL;
Jordan, J;
Dworak, M;
Merkel, T;
Burnstock, G;
(2018)
Myocardial metabolism in heart failure: Purinergic signalling and other metabolic concepts.
Pharmacology & Therapeutics
10.1016/j.pharmthera.2018.08.015.
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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.
| Type: | Article |
|---|---|
| Title: | Myocardial metabolism in heart failure: Purinergic signalling and other metabolic concepts |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.pharmthera.2018.08.015 |
| Publisher version: | https://doi.org/10.1016/j.pharmthera.2018.08.015 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Cardiac metabolism, Heart failure, Insulin resistance, Metabolic therapy, Purinergic signaling |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10060358 |
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