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van der Velden J, Asselbergs FW, Bakkers J, et al. Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC working group on myocardial function and the ESC Working Group on Cellular Biology of the Heart. Cardiovasc Res. 2022;doi: 10.1093/cvr/cvab370.
van der Velden, J., Asselbergs, F. W., Bakkers, J., Batkai, S., Bertrand, L., Bezzina, C. R., Bot, I., Brundel, B., Carrier, L., Chamuleau, S., Ciccarelli, M., Dawson, D., Davidson, S. M., Dendorfer, A., Duncker, D. J., Eschenhagen, T., Fabritz, L., Falcão-Pires, I., Ferdinandy, P., Giacca, M., Girao, H., Gollmann-Tepeköylü, C., Gyongyosi, M., Guzik, T. J., Hamdani, N., Heymans, S., Hilfiker, A., Hilfiker-Kleiner, D., Hoekstra, A. G., Hulot, J. S., Kuster, D. W. D., van Laake, L. W., Lecour, S., Leiner, T., Linke, W. A., Lumens, J., Lutgens, E., Madonna, R., Maegdefessel, L., Mayr, M., van der Meer, P., Passier, R., Perbellini, F., Perrino, C., Pesce, M., Priori, S., Remme, C. A., Rosenhahn, B., Schotten, U., Schulz, R., Sipido, K., Sluijter, J. P. G., van Steenbeek, F., Steffens, S., Terracciano, C. M., Tocchetti, C. G., Vlasman, P., Yeung, K. K., Zacchigna, S., Zwaagman, D., & Thum, T. (2022). Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC working group on myocardial function and the ESC Working Group on Cellular Biology of the Heart. Cardiovascular research, . https://doi.org/10.1093/cvr/cvab370
van der Velden, Jolanda, et al. "Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC working group on myocardial function and the ESC Working Group on Cellular Biology of the Heart." Cardiovascular research vol. (2022). doi: https://doi.org/10.1093/cvr/cvab370
van der Velden J, Asselbergs FW, Bakkers J, Batkai S, Bertrand L, Bezzina CR, Bot I, Brundel B, Carrier L, Chamuleau S, Ciccarelli M, Dawson D, Davidson SM, Dendorfer A, Duncker DJ, Eschenhagen T, Fabritz L, Falcão-Pires I, Ferdinandy P, Giacca M, Girao H, Gollmann-Tepeköylü C, Gyongyosi M, Guzik TJ, Hamdani N, Heymans S, Hilfiker A, Hilfiker-Kleiner D, Hoekstra AG, Hulot JS, Kuster DWD, van Laake LW, Lecour S, Leiner T, Linke WA, Lumens J, Lutgens E, Madonna R, Maegdefessel L, Mayr M, van der Meer P, Passier R, Perbellini F, Perrino C, Pesce M, Priori S, Remme CA, Rosenhahn B, Schotten U, Schulz R, Sipido K, Sluijter JPG, van Steenbeek F, Steffens S, Terracciano CM, Tocchetti CG, Vlasman P, Yeung KK, Zacchigna S, Zwaagman D, Thum T. Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC working group on myocardial function and the ESC Working Group on Cellular Biology of the Heart. Cardiovasc Res. 2022 Jan 06; doi: 10.1093/cvr/cvab370. Epub 2022 Jan 06. PMID: 34999816.
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Cardiovasc Res. 2022 Jan 06; doi: 10.1093/cvr/cvab370. Epub 2022 Jan 06.

Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC working group on myocardial function and the ESC Working Group on Cellular Biology of the Heart.

Cardiovascular research

Jolanda van der Velden, Folkert W Asselbergs, Jeroen Bakkers, Sandor Batkai, Luc Bertrand, Connie R Bezzina, Ilze Bot, Bianca Brundel, Lucie Carrier, Steven Chamuleau, Michele Ciccarelli, Dana Dawson, Sean M Davidson, Andreas Dendorfer, Dirk J Duncker, Thomas Eschenhagen, Larissa Fabritz, Ines Falcão-Pires, Péter Ferdinandy, Mauro Giacca, Henrique Girao, Can Gollmann-Tepeköylü, Mariann Gyongyosi, Tomasz J Guzik, Nazha Hamdani, Stephane Heymans, Andres Hilfiker, Denise Hilfiker-Kleiner, Alfons G Hoekstra, Jean-Sébastien Hulot, Diederik W D Kuster, Linda W van Laake, Sandrine Lecour, Tim Leiner, Wolfgang A Linke, Joost Lumens, Esther Lutgens, Rosalinda Madonna, Lars Maegdefessel, Manuel Mayr, Peter van der Meer, Robert Passier, Filippo Perbellini, Cinzia Perrino, Maurizio Pesce, Silvia Priori, Carol Ann Remme, Bodo Rosenhahn, Ulrich Schotten, Rainer Schulz, Karin Sipido, Joost P G Sluijter, Frank van Steenbeek, Sabine Steffens, Cesare M Terracciano, Carlo Gabriele Tocchetti, Patricia Vlasman, Kak Khee Yeung, Serena Zacchigna, Dayenne Zwaagman, Thomas Thum

Affiliations

  1. Amsterdam UMC, Vrije Universiteit, Physiology, Amsterdam Cardiovascular Science, Amsterdam, The Netherlands.
  2. Netherland Heart Institute, Utrecht, The Netherlands.
  3. Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht,Utrecht University, Utrecht, the Netherlands.
  4. Institute of Cardiovascular Science and Institute of Health Informatics, Faculty of Population Health Sciences, University College London, London, United Kingdom.
  5. Hubrecht Institute-KNAW and University Medical Centre Utrecht, Utrecht, The Netherlands.
  6. Hannover Medical School, Institute of Molecular and Translational Therapeutic Strategies, Hannover, Germany.
  7. Université catholique de Louvain, Institut de Recherche Expérimentale et Clinique, Pole of Cardiovascular Research, Brussels, Belgium.
  8. Heart Center, Department of Experimental Cardiology, Amsterdam UMC, location Academic Medical Center, Amsterdam Cardiovascular Sciences, University of Amsterdam, The Netherlands.
  9. Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden, The Netherlands, University, Leiden.
  10. Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
  11. DZHK (German Centre for Cardiovascular Research),partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
  12. Amsterdam UMC, AMC, Cardiology, Amsterdam Cardiovascular Science, Amsterdam, The Netherlands.
  13. Department of Medicine, Surgery and Odontology, University of Salerno, Italy.
  14. Aberdeen Cardiovascular and Diabetes Centre, Department of Cardiology, Aberdeen Royal Infirmary and University of Aberdeen.
  15. The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX United Kingdom.
  16. Walter-Brendel-Centre of Experimental Medicine, LMU Munich, Marchioninistr. 68, Munich, 81377 Germany, University Hospital.
  17. Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
  18. Institute for Cardiovascular Research, University of Birmingham, and Department of Cardiology, University Hospital Birmingham.
  19. Cardiovascular R&D Center (UnIC), and Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
  20. Cardiometabolic Research Group and MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis Univeristy, Budapest, Hungary.
  21. Pharmahungary Group, Szeged, Hungary.
  22. Department of Medicine, Surgery and Health Sciences and Cardiovascular Department, Centre for Translational Cardiology, Azienda Sanitaria Universitaria Integrata Trieste, Trieste, Italy.
  23. International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
  24. King's British Heart Foundation Centre, King's College London, London, UK.
  25. Univ Coimbra, Center for Innovative Biomedicine and Biotechnology, Faculty of Medicine.
  26. Clinical Academic Centre of Coimbra, Coimbra, Portugal.
  27. Department of Cardiac Surgery, Medical University of Innsbruck, Austria.
  28. Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology, Austria.
  29. Instutute of Cardiovascular and Medical Sciences, University of Glasgow, UK.
  30. Jagiellonian University, Collegium Medicum, Kraków, Poland.
  31. Molecular and Experimental Cardiology, Division Cardiology, Ruhr University Bochum, Bochum, Germany.
  32. Institute of Physiology,Ruhr University Bochum, Bochum, Germany.
  33. Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre,Maastricht University, Maastricht, The Netherlands.
  34. Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
  35. Department for Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Hannover, Germany.
  36. Department for Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
  37. Medical Faculty, Philipps University Marburg, Marburg, Germany.
  38. Computational Science Lab, Informatics Institute, Faculty of Science, University of Amsterdam, the Netherlands.
  39. Université de Paris, INSERM, PARCC, Paris, F-75015 France.
  40. CIC1418 and DMU CARTE, AP-HP, Hôpital Européen Georges-Pompidou, Paris, F-75015 France.
  41. Hatter Institute for Cardiovascular Research in Africa and Cape Heart Institute, department of Medicine, University of Cape Town, south Africa.
  42. Department of Radiology, Utrecht University Medical Center, Utrecht, the Netherlands.
  43. Institute of Physiology II, University of Muenster, Robert-Koch-Str. 27B, Muenster, 48149 Germany.
  44. Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, the Netherlands.
  45. Experimental Vascular Biology Division, Dept. of Medical Biochemistry, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, The Netherlands, Amsterdam.
  46. Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians Universität, München, Germany, DZHK, partner site Munich Heart Alliance, Munich, Germany.
  47. Institute of Cardiology, University of Pisa, Pisa, 56124 Italy.
  48. Department of Internal Medicine, Cardiology Division, University of Texas Medical School, Houston, TX, USA, in.
  49. Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar,Technical University Munich, Munich, Germany.
  50. Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
  51. DZHK, partner Site Munich Heart Alliance, Munich, Germany.
  52. Department of cardiology, university medical center Groningen, university of Groningen, the Netherlands.
  53. Department of Applied Stem Cell Technologies, TechMed Centre, University of Twente, 7500AE Enschede, The Netherlands.
  54. Department of Anatomy and Embryology, Leiden University Medical Centre, 2300 RC The Netherlands, Leiden.
  55. Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
  56. Unità di Ingegneria Tissutale Cardiovascolare. Centro cardiologico Monzino,IRCCS, Milan, Italy.
  57. Molecular Cardiology, Istituti Clinici Scientifici Maugeri, Pavia, Italy.
  58. University of Pavia, Pavia, Italy.
  59. Institute for information Processing,Leibniz University of Hanover, Hannover, 30167 Germany.
  60. Department of Physiology, Cardiovascular Research Institute Maastricht,Maastricht University, the Netherlands.
  61. Institute of Physiology, Justus Liebig University Giessen, Giessen, Germany.
  62. Department of Cardiovascular Sciences, KU Leuven, Leuven, 3000 Belgium.
  63. Department of Cardiology, Experimental Cardiology Laboratory, Regenerative Medicine Center Utrecht, Circulatory Health Laboratory, Utrecht University,University Medical Center Utrecht, The Netherlands.
  64. Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
  65. Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany.
  66. National Heart & Lung Institute, Imperial College London, United Kingdom.
  67. Department of Translational Medical Sciences, Interdepartmental Center of Clinical and Translational Research, Federico II University, Naples, Italy.
  68. Amsterdam UMC, Vrije Universiteit, Surgery, Amsterdam Cardiovascular Science, The Netherlands, Amsterdam.
  69. Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.

PMID: 34999816 DOI: 10.1093/cvr/cvab370

Abstract

Cardiovascular diseases represent a major cause of morbidity and mortality, necessitating research to improve diagnostics, and to discover and test novel preventive and curative therapies. All of which warrant experimental models that recapitulate human disease. The translation of basic science results to clinical practice is a challenging task. In particular for complex conditions such as cardiovascular diseases, which often result from multiple risk factors and co-morbidities. This difficulty might lead some individuals to question the value of animal research, citing the translational 'valley of death', which largely reflects the fact that studies in rodents are difficult to translate to humans. This is also influenced by the fact that new, human-derived in vitro models can recapitulate aspects of disease processes. However, it would be a mistake to think that animal models cannot provide a vital step in the translational pathway as they do provide important pathophysiological insights into disease mechanisms particularly on a organ and systemic level. While stem cell-derived human models have the potential to become key in testing toxicity and effectiveness of new drugs, we need to be realistic, and carefully validate all new human-like disease models. In this position paper, we highlight recent advances in trying to reduce the number of animals for cardiovascular research ranging from stem cell-derived models to in situ modelling of heart properties, bioinformatic models based on large datasets, and improved current animal models, which show clinically relevant characteristics observed in patients with a cardiovascular disease. We aim to provide a guide to help researchers in their experimental design to translate bench findings to clinical routine taking the replacement, reduction and refinement (3R) as a guiding concept.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions please email: [email protected].

Keywords: big data; bioinformatics; cardiovascular disease; co-morbidities; iPSC; multiomics; network medicine; tissue engineering

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