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With a grain of salt: Sodium elevation and metabolic remodelling in heart failure

Research output: Contribution to journalArticlepeer-review

Dunja Aksentijević, Michael J. Shattock

Original languageEnglish
Pages (from-to)106-115
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
PublishedDec 2021

Bibliographical note

Funding Information: DA acknowledges British Heart Foundation Accelerator Award [ AA/18/5/34222 ], Diabetes UK Grant ( 19/0005973 ), Barts Charity Grant ( MRC 0215 ), Wellcome Trust [ 221604/Z/20/Z ] for funding her work. MJS: British Heart Foundation Programme Grant [ RG/12/4/29426 ]. Publisher Copyright: © 2021 Elsevier Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Elevated intracellular Na (Nai) and metabolic impairment are interrelated pathophysiological features of the failing heart (HF). There have been a number of studies showing that myocardial sodium elevation subtly affects mitochondrial function. During contraction, mitochondrial calcium (Camito) stimulates a variety of TCA cycle enzymes, thereby providing reducing equivalents to maintain ATP supply. Nai elevation has been shown to impact Camito; however, whether metabolic remodelling in HF is caused by increased Nai has only been recently demonstrated. This novel insight may help to elucidate the contribution of metabolic remodelling in the pathophysiology of HF, the lack of efficacy of current HF therapies and a rationale for the development of future metabolism-targeting treatments. Here we review the relationship between Na pump inhibition, elevated Nai, and altered metabolic profile in the context of HF and their link to metabolic (in)flexibility and mitochondrial reprogramming.

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