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Assessment of left ventricular tissue mitochondrial bioenergetics in patients with stable coronary artery disease.
Jones, Richard E; Gruszczyk, Anja V; Schmidt, Christina; Hammersley, Daniel J; Mach, Lukas; Lee, Michael; Wong, Joyce; Yang, Ming; Hatipoglu, Suzan; Lota, Amrit S; Barnett, Sam N; Toscano-Rivalta, Rebecca; Owen, Ruth; Raja, Shahzad; De Robertis, Fabio; Smail, Hassiba; De-Souza, Anthony; Stock, Ulrich; Kellman, Peter; Griffin, Julian; Dumas, Marc-Emmanuel; Martin, Jack L; Saeb-Parsy, Kourosh; Vazir, Ali; Cleland, John G F; Pennell, Dudley J; Bhudia, Sunil K; Halliday, Brian P; Noseda, Michela; Frezza, Christian; Murphy, Michael P; Prasad, Sanjay K.
Afiliação
  • Jones RE; National Heart and Lung Institute, Imperial College London, London, UK.
  • Gruszczyk AV; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Schmidt C; Anglia Ruskin University, Chelmsford, UK.
  • Hammersley DJ; Essex Cardiothoracic Centre, Basildon, UK.
  • Mach L; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
  • Lee M; MRC Cancer Unit, University of Cambridge, Cambridge, UK.
  • Wong J; National Heart and Lung Institute, Imperial College London, London, UK.
  • Yang M; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Hatipoglu S; National Heart and Lung Institute, Imperial College London, London, UK.
  • Lota AS; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Barnett SN; National Heart and Lung Institute, Imperial College London, London, UK.
  • Toscano-Rivalta R; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Owen R; MRC Cancer Unit, University of Cambridge, Cambridge, UK.
  • Raja S; University of Cologne, CECAD, Cologne, Germany.
  • De Robertis F; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Smail H; National Heart and Lung Institute, Imperial College London, London, UK.
  • De-Souza A; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Stock U; National Heart and Lung Institute, Imperial College London, London, UK.
  • Kellman P; National Heart and Lung Institute, Imperial College London, London, UK.
  • Griffin J; Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
  • Dumas ME; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Martin JL; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Saeb-Parsy K; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Vazir A; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Cleland JGF; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
  • Pennell DJ; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD USA.
  • Bhudia SK; The Rowett Institute, University of Aberdeen, Aberdeen, UK.
  • Halliday BP; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Noseda M; National Heart and Lung Institute, Imperial College London, London, UK.
  • Frezza C; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Murphy MP; European Genomic Institute of Diabetes, INSERM U1283, CNRS 8199, Institut Pasteur de Lille, Lille University Hospital, University of Lille, Lille, France.
  • Prasad SK; McGill Genome Centre, McGill University, Montréal, QC Canada.
Nat Cardiovasc Res ; 2(8): 733-745, 2023.
Article em En | MEDLINE | ID: mdl-38666037
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 ATPADP 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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Nat Cardiovasc Res Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Nat Cardiovasc Res Ano de publicação: 2023 Tipo de documento: Article