The Efficacy of risk factor modification compared to NAD+ repletion in diastolic heart failure

Yen Chin Koay; Ren Ping Liu; Bailey McIntosh; Niv Vigder; Serlin Lauren; Angela Yu Bai; Saki Tomita; Desmond Li; Dylan Harney; Benjamin Hunter; Yunwei Zhang; Jean Yang; Paul Bannon; Ashleigh Philp; Andrew Philp; David M. Kaye; Mark Larance; Sean Lal; John F. O'Sullivan

doi:10.1016/j.jacbts.2024.01.011

The Efficacy of risk factor modification compared to NAD⁺ repletion in diastolic heart failure

Yen Chin Koay^*, Ren Ping Liu, Bailey McIntosh, Niv Vigder, Serlin Lauren, Angela Yu Bai, Saki Tomita, Desmond Li, Dylan Harney, Benjamin Hunter, Yunwei Zhang, Jean Yang, Paul Bannon, Ashleigh Philp, Andrew Philp, David M. Kaye, Mark Larance, Sean Lal, John F. O'Sullivan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

59 Downloads (Pure)

Abstract

Heart failure (HF) with left ventricular diastolic dysfunction is a growing global concern. This study evaluated myocardial oxidized nicotinamide adenine dinucleotide (NAD⁺) levels in human systolic and diastolic HF and in a murine model of HF with preserved ejection fraction, exploring NAD⁺ repletion as therapy. We quantified myocardial NAD⁺ and nicotinamide phosphoribosyltransferase levels, assessing restoration with nicotinamide riboside (NR). Findings show significant NAD⁺ and nicotinamide phosphoribosyltransferase depletion in human diastolic HF myocardium, but NR successfully restored NAD⁺ levels. In murine HF with preserved ejection fraction, NR as preventive and therapeutic intervention improved metabolic and antioxidant profiles. This study underscores NAD⁺ repletion's potential in diastolic HF management.

Original language	English
Pages (from-to)	733-750
Number of pages	18
Journal	JACC: Basic to Translational Science
Volume	9
Issue number	6
Early online date	20 Mar 2024
DOIs	https://doi.org/10.1016/j.jacbts.2024.01.011
Publication status	Published - Jun 2024
Externally published	Yes

Bibliographical note

© 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

diastolic heart failure
heart failure
NAD+ repletion

Access to Document

10.1016/j.jacbts.2024.01.011Licence: CC BY-NC-ND

Publisher version (open access)Final published version, 3.9 MBLicence: CC BY-NC-ND

Cite this

Koay, Y. C., Liu, R. P., McIntosh, B., Vigder, N., Lauren, S., Bai, A. Y., Tomita, S., Li, D., Harney, D., Hunter, B., Zhang, Y., Yang, J., Bannon, P., Philp, A., Philp, A., Kaye, D. M., Larance, M., Lal, S., & O'Sullivan, J. F. (2024). The Efficacy of risk factor modification compared to NAD⁺ repletion in diastolic heart failure. JACC: Basic to Translational Science, 9(6), 733-750. https://doi.org/10.1016/j.jacbts.2024.01.011

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title = "The Efficacy of risk factor modification compared to NAD+ repletion in diastolic heart failure",

abstract = "Heart failure (HF) with left ventricular diastolic dysfunction is a growing global concern. This study evaluated myocardial oxidized nicotinamide adenine dinucleotide (NAD+) levels in human systolic and diastolic HF and in a murine model of HF with preserved ejection fraction, exploring NAD+ repletion as therapy. We quantified myocardial NAD+ and nicotinamide phosphoribosyltransferase levels, assessing restoration with nicotinamide riboside (NR). Findings show significant NAD+ and nicotinamide phosphoribosyltransferase depletion in human diastolic HF myocardium, but NR successfully restored NAD+ levels. In murine HF with preserved ejection fraction, NR as preventive and therapeutic intervention improved metabolic and antioxidant profiles. This study underscores NAD+ repletion's potential in diastolic HF management.",

keywords = "diastolic heart failure, heart failure, NAD+ repletion",

author = "Koay, {Yen Chin} and Liu, {Ren Ping} and Bailey McIntosh and Niv Vigder and Serlin Lauren and Bai, {Angela Yu} and Saki Tomita and Desmond Li and Dylan Harney and Benjamin Hunter and Yunwei Zhang and Jean Yang and Paul Bannon and Ashleigh Philp and Andrew Philp and Kaye, {David M.} and Mark Larance and Sean Lal and O'Sullivan, {John F.}",

note = "{\textcopyright} 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

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Koay, YC, Liu, RP, McIntosh, B, Vigder, N, Lauren, S, Bai, AY, Tomita, S, Li, D, Harney, D, Hunter, B, Zhang, Y, Yang, J, Bannon, P, Philp, A, Philp, A, Kaye, DM, Larance, M, Lal, S & O'Sullivan, JF 2024, 'The Efficacy of risk factor modification compared to NAD⁺ repletion in diastolic heart failure', JACC: Basic to Translational Science, vol. 9, no. 6, pp. 733-750. https://doi.org/10.1016/j.jacbts.2024.01.011

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AU - Koay, Yen Chin

AU - Liu, Ren Ping

AU - McIntosh, Bailey

AU - Vigder, Niv

AU - Lauren, Serlin

AU - Bai, Angela Yu

AU - Tomita, Saki

AU - Li, Desmond

AU - Harney, Dylan

AU - Hunter, Benjamin

AU - Zhang, Yunwei

AU - Yang, Jean

AU - Bannon, Paul

AU - Philp, Ashleigh

AU - Philp, Andrew

AU - Kaye, David M.

AU - Larance, Mark

AU - Lal, Sean

AU - O'Sullivan, John F.

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AB - Heart failure (HF) with left ventricular diastolic dysfunction is a growing global concern. This study evaluated myocardial oxidized nicotinamide adenine dinucleotide (NAD+) levels in human systolic and diastolic HF and in a murine model of HF with preserved ejection fraction, exploring NAD+ repletion as therapy. We quantified myocardial NAD+ and nicotinamide phosphoribosyltransferase levels, assessing restoration with nicotinamide riboside (NR). Findings show significant NAD+ and nicotinamide phosphoribosyltransferase depletion in human diastolic HF myocardium, but NR successfully restored NAD+ levels. In murine HF with preserved ejection fraction, NR as preventive and therapeutic intervention improved metabolic and antioxidant profiles. This study underscores NAD+ repletion's potential in diastolic HF management.

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