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Assessment of left ventricular tissue mitochondrial bioenergetics in patients with stable coronary artery disease

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posted on 2024-01-05, 10:09 authored by Richard E Jones, Anja V Gruszczyk, Christina Schmidt, Daniel J Hammersley, Lukas Mach, Michael Lee, Joyce Wong, Ming Yang, Suzan Hatipoglu, Amrit S Lota, Sam N Barnett, Rebecca Toscano-Rivalta, Ruth Owen, Shahzad Raja, Fabio De Robertis, Hassiba Smail, Anthony De-Souza, Ulrich Stock, Peter Kellman, Julian Griffin, Marc-Emmanuel Dumas, Jack L Martin, Kourosh Saeb-Parsy, Ali Vazir, John GF Cleland, Dudley J Pennell, Sunil K Bhudia, Brian P Halliday, Michela Noseda, Christian Frezza, Michael P Murphy, Sanjay K Prasad

Recurrent myocardial ischemia can lead to left ventricular (LV) dysfunction in patients with coronary artery disease (CAD). In this observational cohort study, we assessed for chronic metabolomic and transcriptomic adaptations within LV myocardium of patients undergoing coronary artery bypass grafting. During surgery, paired transmural LV biopsies were acquired on the beating heart from regions with and without evidence of inducible ischemia on preoperative stress perfusion cardiovascular magnetic resonance. From 33 patients, 63 biopsies were acquired, compared to analysis of LV samples from 11 donor hearts. The global myocardial adenosine triphosphate (ATP):adenosine diphosphate (ADP) ratio was reduced in patients with CAD as compared to donor LV tissue, with increased expression of oxidative phosphorylation (OXPHOS) genes encoding the electron transport chain complexes across multiple cell types. Paired analyses of biopsies obtained from LV segments with or without inducible ischemia revealed no significant difference in the ATP:ADP ratio, broader metabolic profile or expression of ventricular cardiomyocyte genes implicated in OXPHOS. Differential metabolite analysis suggested dysregulation of several intermediates in patients with reduced LV ejection fraction, including succinate. Overall, our results suggest that viable myocardium in patients with stable CAD has global alterations in bioenergetic and transcriptional profile without large regional differences between areas with or without inducible ischemia.

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Refereed

  • Yes

Volume

2

Page range

733-745

Publication title

Nature Cardiovascular Research

ISSN

2731-0590

Publisher

Springer Science and Business Media LLC

Language

  • eng

Item sub-type

Journal Article

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  • School of Life Sciences Outputs

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