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Is there a causal link between intracellular na elevation and metabolic remodelling in cardiac hypertrophy?

Research output: Contribution to journalReview article

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Is there a causal link between intracellular na elevation and metabolic remodelling in cardiac hypertrophy? / Aksentijevic, Dunja; O’Brien, Brett A.; Eykyn, Thomas R.; Shattock, Michael J.

In: Biochemical Society Transactions, Vol. 46, No. 4, 03.07.2018, p. 817-827.

Research output: Contribution to journalReview article

Harvard

Aksentijevic, D, O’Brien, BA, Eykyn, TR & Shattock, MJ 2018, 'Is there a causal link between intracellular na elevation and metabolic remodelling in cardiac hypertrophy?', Biochemical Society Transactions, vol. 46, no. 4, pp. 817-827. https://doi.org/10.1042/BST20170508

APA

Aksentijevic, D., O’Brien, B. A., Eykyn, T. R., & Shattock, M. J. (2018). Is there a causal link between intracellular na elevation and metabolic remodelling in cardiac hypertrophy? Biochemical Society Transactions, 46(4), 817-827. https://doi.org/10.1042/BST20170508

Vancouver

Aksentijevic D, O’Brien BA, Eykyn TR, Shattock MJ. Is there a causal link between intracellular na elevation and metabolic remodelling in cardiac hypertrophy? Biochemical Society Transactions. 2018 Jul 3;46(4):817-827. https://doi.org/10.1042/BST20170508

Author

Aksentijevic, Dunja ; O’Brien, Brett A. ; Eykyn, Thomas R. ; Shattock, Michael J. / Is there a causal link between intracellular na elevation and metabolic remodelling in cardiac hypertrophy?. In: Biochemical Society Transactions. 2018 ; Vol. 46, No. 4. pp. 817-827.

Bibtex Download

@article{50a30f38c87d4a249d03342a3f15c6c0,
title = "Is there a causal link between intracellular na elevation and metabolic remodelling in cardiac hypertrophy?",
abstract = "Alterations in excitation–contraction 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 is 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 elevation 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.",
author = "Dunja Aksentijevic and O’Brien, {Brett A.} and Eykyn, {Thomas R.} and Shattock, {Michael J.}",
year = "2018",
month = "7",
day = "3",
doi = "10.1042/BST20170508",
language = "English",
volume = "46",
pages = "817--827",
journal = "Biochemical Society Transactions",
issn = "0300-5127",
publisher = "Portland Press Ltd.",
number = "4",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Is there a causal link between intracellular na elevation and metabolic remodelling in cardiac hypertrophy?

AU - Aksentijevic, Dunja

AU - O’Brien, Brett A.

AU - Eykyn, Thomas R.

AU - Shattock, Michael J.

PY - 2018/7/3

Y1 - 2018/7/3

N2 - Alterations in excitation–contraction 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 is 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 elevation 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.

AB - Alterations in excitation–contraction 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 is 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 elevation 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.

UR - http://www.scopus.com/inward/record.url?scp=85052112694&partnerID=8YFLogxK

U2 - 10.1042/BST20170508

DO - 10.1042/BST20170508

M3 - Review article

AN - SCOPUS:85052112694

VL - 46

SP - 817

EP - 827

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

SN - 0300-5127

IS - 4

ER -

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