Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

Cardiovascular Research (2017) 113, 564–585 doi:10.1093/cvr/cvx049 Derek J. Hausenloy1*†, David Garcia-Dorado2†, Hans Erik Bøtker3, Sean M. Davidson4, James Downey5, Felix B. Engel6, Robert Jennings7, Sandrine Lecour8, Jonathan Leor9, Rosalinda Madonna10, Michel Ovize11, Cinzia Perrino12, Fabrice Prunier13, Rainer Schulz14, Joost P.G. Sluijter15, Linda W. Van Laake16, Jakob Vinten-Johansen17, Derek M. Yellon18, Kirsti Ytrehus19, Gerd Heusch20‡, and Péter Ferdinandy21*‡ 1 The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London WC1E 6HX, UK; The National Institute of Health Research University College London Hospitals Biomedical Research Centre, 149 Tottenham Court Road London, W1T 7DN, UK; Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, 8 College Road, Singapore 169857; National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Dr, Singapore 169609, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore; Barts Heart Centre, St Bartholomew’s Hospital, London, UK; 2Department of Cardiology, Vall d Hebron University Hospital and Research Institute. Universitat Aut onoma, Passeig de la Vall d’Hebron, 119-129, 08035 Barcelona, Spain; 3Department of Cardiology, Aarhus University Hospital Skejby, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark; 4The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London WC1E 6HX, UK; 5Department of Physiology and Cell Biology, College of Medicine, University of South Alabama, 5851 USA Dr. N., MSB 3074, Mobile, AL 36688, USA; 6Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universit€at Erlangen-Nßrnberg, Schloßplatz 4, 91054 Erlangen, Germany; 7Department of Cardiology, Duke University, Durham, NC 27708, USA; 8Department of Medicine, Hatter Institute for Cardiovascular Research in Africa and South African Medical Research Council Inter-University Cape Heart Group, Faculty of Health Sciences, University of Cape Town, Chris Barnard Building, Anzio Road, Observatory, 7925, Cape Town, Western Cape, South Africa; 9Tamman Cardiovascular Research Institute, Sheba Medical Center, Tel Hashomer, Israel; Neufeld Cardiac Research Institute, Tel-Aviv University, Sheba Medical Center, Tel Hashomer, 5265601, Israel; Sheba Center for Regenerative Medicine, Stem Cell, and Tissue Engineering, Tel Hashomer, 5265601, Israel; 10Center of Aging Sciences and Translational Medicine – CESI-MeT, “G. d’Annunzio” University, Chieti, Italy; Institute of Cardiology, Department of Neurosciences, Imaging, and Clinical Sciences, “G. d’Annunzio University, Chieti, Italy; Texas Heart Institute and University of Texas Medical School in Houston, Department of Internal Medicine, 6770 Bertner Avenue, Houston, Texas 77030 USA; 11Explorations Fonctionnelles Cardiovasculaires, Hôpital Louis Pradel, 28 Avenue du Doyen Jean Lépine, 69500 Bron, France; UMR 1060 (CarMeN), Université Claude Bernard Lyon, 43 Boulevard du 11 Novembre 1918, 69100 Villeurbanne, France; 12Department of Advanced Biomedical Sciences, Division of Cardiology, Federico II University Corso Umberto I, 40, 80138 Napoli, Italy; 13Department of Cardiology, University of Angers, University Hospital of Angers, 4 Rue Larrey, 49100 Angers, France; 14Institute of Physiology, Justus-Liebig, University of Giessen, Ludwigstraße 23, 35390 Gießen, Germany; 15Cardiology and UMC Utrecht Regenerative Medicine Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands; 16 Division Heart and Lungs, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands; 17Division of Cardiothoracic Surgery, Department of Surgery, Emory University, 201 Dowman Dr, Atlanta, GA 30322, USA; 18The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London WC1E 6HX, UK; The National Institute of Health Research University College London Hospitals Biomedical Research Centre, 149 Tottenham Court Road London, W1T 7DN, UK; 19Cardiovascular Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Hansine Hansens veg 18, 9019 Tromsø, Norway; 20Institute for Pathophysiology, West-German Heart and Vascular Center, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany; and 21Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Nagyvarad tér 4, 1089 Hungary; Pharmahungary Group, Graphisoft Park, 7 Zahony street, Budapest, H-1031, Hungary Received 2 October 2016; revised 3 December 2016; editorial decision 26 December 2016; accepted 15 March 2017; online publish-ahead-of-print 17 March 2017 Time for primary review: 43 days Abstract Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments * Corresponding author. Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, 8 College Road, Singapore 169857. Tel: þ65 66015121/65166719, E-mail: (D.H.) and Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary. E-mail: (P.F.) † The first two authors contributed equally to the paper as joint first authors. ‡ The last two authors contributed equally to the paper as joint senior authors. C The Author 2017. The last two authors contributed equally to the paper as joint senior authors. Published on behalf of the European Society of Cardiology. All rights reserved. V For permissions, please email: . Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart 565 ESC WG Position Paper on cardioprotection have been tested in the clinic—however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing. Therefore, in this Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart, we critically analyse the current state of ischaemic conditioning in both the experimental and clinical settings, provide recommendations for improving its translation into the clinical setting, and highlight novel therapeutic targets and new treatment strategies for reducing acute myocardial IRI. 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 䊏 (...truncated)