Jones, R. E. et al. (2023) Assessment of left ventricular tissue mitochondrial bioenergetics in patients with stable coronary artery disease. Nature Cardiovascular Research, 2(8), pp. 733-745. (doi: 10.1038/s44161-023-00312-z)
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Abstract
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.
| Item Type: | Articles |
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| Additional Information: | This work was supported by a National Heart and Lung Institute Foundation grant awarded to S.K.P., R.E.J. and D.J.H. Additionally, the study was supported by an Intermediate Clinical Research Fellowship awarded to B.P.H. (FS/ICRF/21/26019). Work in the M.P.M. laboratory was supported by the Medical Research Council UK (MC_UU_00015/3) and by a Wellcome Trust Investigator award (220257/Z/20/Z). M.E.D. is funded by the NIHR Imperial Biomedical Research Centre; by grants from the French National Research Agency (ANR-10-LABX-46 (European Genomics Institute for Diabetes)); by the National Center for Precision Diabetic Medicine–PreciDIAB, which is jointly supported by the French National Agency for Research (ANR-18-IBHU-0001); by the European Union (FEDER); by the Hauts-de-France Regional Council (agreement 20001891/NP0025517); by the European Metropolis of Lille (agreement 2019_ESR_11); by Isite ULNE (R-002–20-TALENT-DUMAS), also jointly funded by ANR (ANR-16-IDEX-0004-ULNE); and by the Hauts-de-France Regional Council (20002845). This work was, in part, supported by a grant to M.N. from the British Heart Foundation and Deutsches Zentrum für Herz-Kreislauf-Forschung (BHF/DZHK) (SP/19/1/34461) and by a grant from the Chan Zuckerberg Foundation (2019-202666, M.N.). A National Heart and Lung Institute PhD studentship to M.N. supports S.N.B. L.M. is supported by a British Society for Heart Failure Research Fellowship. C.F. is supported by the Medical Research Council UK (MRC_MC_UU_12022/6), the CRUK Programme Foundation award (C51061/A27453), an ERC Consolidator Grant (ONCOFUM, ERC819920) and by the Alexander von Humboldt Foundation in the framework of the Alexander von Humboldt Professorship, endowed by the Federal Ministry of Education and Research. The work of C.S. was funded by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie grant agreement number 722605 and the Alexander von Humboldt Professorship to C.F. J.G.F.C. is supported by British Heart Foundation Centre of Research Excellence award RE/18/6/34217. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Cleland, Professor John |
| Authors: | Jones, R. E., Gruszczyk, A. V., Schmidt, C., Hammersley, D. J., Mach, L., Lee, M., Wong, J., Yang, M., Hatipoglu, S., Lota, A. S., Barnett, S. N., Toscano-Rivalta, R., Owen, R., Raja, S., De Robertis, F., Smail, H., De-Souza, A., Stock, U., Kellman, P., Griffin, J., Dumas, M.-E., Martin, J. L., Saeb-Parsy, K., Vazir, A., Cleland, J. G.F., Pennell, D. J., Bhudia, S. K., Kalliday, B. P., Noseda, M., Frezza, C., Murphy, M. P., and Prasad, S. K. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre |
| Journal Name: | Nature Cardiovascular Research |
| Publisher: | Springer Nature |
| ISSN: | 2731-0590 |
| ISSN (Online): | 2731-0590 |
| Published Online: | 07 August 2023 |
| Copyright Holders: | Copyright © 2023 The Authors |
| First Published: | First published in Nature Cardiovascular Research 2(8): 733-745 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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