PDF(Pubmed)
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 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.
摘要：
心血管疾病是发病率和死亡率的主要原因，需要研究以改善诊断，并发现和测试新的预防和治疗疗法，所有这些都需要概括人类疾病的实验模型。将基础科学成果转化为临床实践是一项具有挑战性的任务，特别是对于复杂的疾病，如心血管疾病，这通常是由多种风险因素和合并症引起的。这种困难可能会导致一些人质疑动物研究的价值，引用翻译的“死亡之谷”，这在很大程度上反映了这样一个事实，即对啮齿动物的研究很难转化为人类。这也受到新的影响，人类来源的体外模型可以概括疾病过程的各个方面。然而,认为动物模型并不代表翻译途径的重要步骤是错误的，因为它们确实提供了对疾病机制的重要病理生理学见解，特别是在器官和系统水平上。虽然干细胞衍生的人体模型有可能成为测试新药毒性和有效性的关键，我们需要现实一点，并仔细验证所有新的类似人类的疾病模型。在这份立场文件中，我们强调了最近在减少心血管研究动物数量方面的进展，从干细胞衍生模型到心脏特性的原位建模，基于大型数据集的生物信息学模型，和最先进的动物模型，显示在心血管疾病患者中观察到的临床相关特征。我们的目标是提供一个指导，以帮助研究人员在他们的实验设计中，将实验结果转化为临床常规，reduction,和细化(3R)作为指导概念。
