@article{3077507,
    title = "Cardiac metabolism as a driver and therapeutic target of myocardial infarction",
    author = "Zuurbier, C.J. and Bertrand, L. and Beauloye, C.R. and Andreadou, I. and Ruiz-Meana, M. and Jespersen, N.R. and Kula-Alwar, D. and Prag, H.A. and Eric Botker, H. and Dambrova, M. and Montessuit, C. and Kaambre, T. and Liepinsh, E. and Brookes, P.S. and Krieg, T.",
    journal = "Journal of Cellular and Molecular Medicine",
    year = "2020",
    volume = "24",
    number = "11",
    pages = "5937-5954",
    publisher = "Blackwell Publishing Inc.",
    issn = "1582-1838, 1582-4934",
    doi = "10.1111/jcmm.15180",
    keywords = "3 hydroxybutyric acid;  adenosine triphosphatase;  adenylate kinase;  aspartic acid;  CD36 antigen;  creatine kinase;  creatine phosphate;  cyclophilin D;  glucosamine;  glucose transporter 1;  glucose transporter 4;  glutamine;  hexokinase;  hexokinase 2;  hexosamine;  ketone;  long chain fatty acid;  lysine;  malic acid;  malonyl coenzyme A decarboxylase;  monocarboxylate transporter 1;  pyruvate dehydrogenase;  reactive oxygen metabolite;  sirtuin 1;  sirtuin 3;  sirtuin 5;  succinic acid;  triacylglycerol;  tricarboxylic acid;  unclassified drug;  unindexed drug, acetylation;  AMPK signaling;  biosynthesis;  cardiotoxicity;  cryoelectron microscopy;  cytoskeleton;  deacetylation;  energy transfer;  fatty acid metabolism;  fatty acid oxidation;  glucose oxidation;  glycolysis;  heart failure;  heart infarction;  heart infarction size;  heart mitochondrion;  heart muscle metabolism;  heart muscle necrosis;  heart protection;  human;  inner membrane;  mitochondrial respiration;  myocardial ischemia reperfusion injury;  nonhuman;  oxidative phosphorylation;  oxygen consumption;  pathophysiology;  priority journal;  protein expression;  Review;  risk factor;  ST segment elevation myocardial infarction;  animal;  cardiac muscle;  energy metabolism;  heart infarction;  metabolism;  molecularly targeted therapy;  pathology, Animals;  Energy Metabolism;  Humans;  Mitochondria, Heart;  Molecular Targeted Therapy;  Myocardial Infarction;  Myocardial Reperfusion Injury;  Myocardium",
    abstract = "Reducing infarct size during a cardiac ischaemic-reperfusion episode is still of paramount importance, because the extension of myocardial necrosis is an important risk factor for developing heart failure. Cardiac ischaemia-reperfusion injury (IRI) is in principle a metabolic pathology as it is caused by abruptly halted metabolism during the ischaemic episode and exacerbated by sudden restart of specific metabolic pathways at reperfusion. It should therefore not come as a surprise that therapy directed at metabolic pathways can modulate IRI. Here, we summarize the current knowledge of important metabolic pathways as therapeutic targets to combat cardiac IRI. Activating metabolic pathways such as glycolysis (eg AMPK activators), glucose oxidation (activating pyruvate dehydrogenase complex), ketone oxidation (increasing ketone plasma levels), hexosamine biosynthesis pathway (O-GlcNAcylation; administration of glucosamine/glutamine) and deacetylation (activating sirtuins 1 or 3; administration of NAD+-boosting compounds) all seem to hold promise to reduce acute IRI. In contrast, some metabolic pathways may offer protection through diminished activity. These pathways comprise the malate-aspartate shuttle (in need of novel specific reversible inhibitors), mitochondrial oxygen consumption, fatty acid oxidation (CD36 inhibitors, malonyl-CoA decarboxylase inhibitors) and mitochondrial succinate metabolism (malonate). Additionally, protecting the cristae structure of the mitochondria during IR, by maintaining the association of hexokinase II or creatine kinase with mitochondria, or inhibiting destabilization of FOF1-ATPase dimers, prevents mitochondrial damage and thereby reduces cardiac IRI. Currently, the most promising and druggable metabolic therapy against cardiac IRI seems to be the singular or combined targeting of glycolysis, O-GlcNAcylation and metabolism of ketones, fatty acids and succinate. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd"
}