{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:40:32Z","timestamp":1787762432240,"version":"build-2784847793"},"reference-count":82,"publisher":"Portland Press Ltd.","issue":"4","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":387,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,8,20]]},"abstract":"<jats:p>Alterations in excitation\u2013contraction coupling and elevated intracellular sodium (Nai) are hallmarks of pathological cardiac remodelling that underline contractile dysfunction. In addition, changes in cardiac metabolism are observed in cardiac hypertrophy and heart failure (HF) that lead to a mismatch in ATP supply and demand, contributing to poor prognosis. A link between Nai and altered metabolism has been proposed but is not well understood. Many mitochondrial enzymes are stimulated by mitochondrial calcium (Camito) during contraction, thereby sustaining production of reducing equivalents to maintain ATP supply. This stimulation is thought to be perturbed when cytosolic Nai\u00a0is high due to increased Camito efflux, potentially compromising ATPmito production and leading to metabolic dysregulation. Increased Nai has been previously shown to affect Camito; however, whether Nai\u00a0elevation plays a causative role in energetic mismatching in the hypertrophied and failing heart remains unknown. In this review, we discuss the relationship between elevated Nai, NaK ATPase dysregulation and the metabolic phenotype in the contexts of pathological hypertrophy and HF and their link to metabolic flexibility, capacity (reserve) and efficiency that are governed by intracellular ion homeostasis. The development of non-invasive analytical techniques using nuclear magnetic resonance able to probe metabolism in situ in the functioning heart will enable a better understanding of the underlying mechanisms of Nai overload in cardiac pathophysiology. They will lead to novel insights that help to explain the metabolic contribution towards these diseases, the incomplete rescue observed with current therapies and a rationale for future energy-targeted therapies.<\/jats:p>","DOI":"10.1042\/bst20170508","type":"journal-article","created":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T14:35:26Z","timestamp":1530628526000},"page":"817-827","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Is there a causal link between intracellular Na elevation and metabolic remodelling in cardiac hypertrophy?"],"prefix":"10.1042","volume":"46","author":[{"given":"Dunja","family":"Aksentijevic","sequence":"first","affiliation":[{"name":"School of Biological and Chemical Sciences, Queen Mary University of London, G.E. Fogg Building, London, U.K."},{"name":"King's College London, School of Cardiovascular and Medical Sciences, British Heart Foundation Centre of Research Excellence, St Thomas Hospital, London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett A.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"King's College London, School of Cardiovascular and Medical Sciences, British Heart Foundation Centre of Research Excellence, St Thomas Hospital, London, U.K."},{"name":"Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas\u2019 Hospital, London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Eykyn","sequence":"additional","affiliation":[{"name":"Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas\u2019 Hospital, London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Shattock","sequence":"additional","affiliation":[{"name":"King's College London, School of Cardiovascular and Medical Sciences, British Heart Foundation Centre of Research Excellence, St Thomas Hospital, London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,7,3]]},"reference":[{"key":"2021111818021530600_BST-2017-0508CC1","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.coph.2008.12.015","article-title":"Phospholemman: its role in normal cardiac physiology and potential as a drugable target in disease","volume":"9","author":"Shattock","year":"2009","journal-title":"Curr. 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