Animal models and animal-free innovations for cardiovascular research

TY - JOUR

T1 - Animal models and animal-free innovations for cardiovascular research

T2 - 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

AU - van der Velden, Jolanda

AU - Asselbergs, Folkert W

AU - Bakkers, Jeroen

AU - Batkai, Sandor

AU - Bertrand, Luc

AU - Bezzina, Connie R

AU - Bot, Ilze

AU - Brundel, Bianca J J M

AU - Carrier, Lucie

AU - Chamuleau, Steven

AU - Ciccarelli, Michele

AU - Dawson, Dana

AU - Davidson, Sean M

AU - Dendorfer, Andreas

AU - Duncker, Dirk J

AU - Eschenhagen, Thomas

AU - Fabritz, Larissa

AU - Falcão-Pires, Ines

AU - Ferdinandy, Péter

AU - Giacca, Mauro

AU - Girao, Henrique

AU - Gollmann-Tepeköylü, Can

AU - Gyongyosi, Mariann

AU - Guzik, Tomasz J

AU - Hamdani, Nazha

AU - Heymans, Stephane

AU - Hilfiker, Andres

AU - Hilfiker-Kleiner, Denise

AU - Hoekstra, Alfons G

AU - Hulot, Jean-Sébastien

AU - Kuster, Diederik W D

AU - van Laake, Linda W

AU - Lecour, Sandrine

AU - Leiner, Tim

AU - Linke, Wolfgang A

AU - Lumens, Joost

AU - Lutgens, Esther

AU - Madonna, Rosalinda

AU - Maegdefessel, Lars

AU - Mayr, Manuel

AU - van der Meer, Peter

AU - Passier, Robert

AU - Perbellini, Filippo

AU - Perrino, Cinzia

AU - Pesce, Maurizio

AU - Priori, Silvia

AU - Remme, Carol Ann

AU - Rosenhahn, Bodo

AU - Schotten, Ulrich

AU - Schulz, Rainer

AU - Sipido, Karin R

AU - Sluijter, Joost P G

AU - van Steenbeek, Frank

AU - Steffens, Sabine

AU - Terracciano, Cesare M

AU - Tocchetti, Carlo Gabriele

AU - Vlasman, Patricia

AU - Yeung, Kak Khee

AU - Zacchigna, Serena

AU - Zwaagman, Dayenne

AU - Thum, Thomas

AU - ESC Working Group onMyocardial Function / ESC Working Group on Cellular Biology of the Heart

N1 - Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.

PY - 2022/12/9

Y1 - 2022/12/9

N2 - 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 comorbidities. 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 do not represent a vital step in the translational pathway as they do provide important pathophysiological insights into disease mechanisms particularly on an 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 state-of-the-art 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.

AB - 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 comorbidities. 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 do not represent a vital step in the translational pathway as they do provide important pathophysiological insights into disease mechanisms particularly on an 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 state-of-the-art 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.

KW - Humans

KW - Animals

KW - Cardiovascular Diseases/diagnosis

KW - Research Design

KW - Models, Animal

U2 - 10.1093/cvr/cvab370

DO - 10.1093/cvr/cvab370

M3 - SCORING: Review article

C2 - 34999816

VL - 118

SP - 3016

EP - 3051

JO - CARDIOVASC RES

JF - CARDIOVASC RES

SN - 0008-6363

IS - 15

ER -