Heart disease is the leading cause of death worldwide. Despite decades of research, most heart pathologies have limited treatments, and often the only curative approach is heart transplantation. Thus, there is an urgent need to develop new therapeutic approaches for treating cardiac diseases. Animal models that reproduce the human pathophysiology are essential to uncovering the biology of diseases and discovering therapies. Traditionally, mammals have been used as models of cardiac disease, but the cost of generating and maintaining new models is exorbitant, and the studies have very low throughput. In the last decade, the zebrafish has emerged as a tractable model for cardiac diseases, owing to several characteristics that made this animal popular among developmental biologists. Zebrafish fertilization and development are external; embryos can be obtained in high numbers, are cheap and easy to maintain, and can be manipulated to create new genetic models. Moreover, zebrafish exhibit an exceptional ability to regenerate their heart after injury. This review summarizes 25 years of research using the zebrafish to study the heart, from the classical forward screenings to the contemporary methods to model mutations found in patients with cardiac disease. We discuss the advantages and limitations of this model organism and introduce the experimental approaches exploited in zebrafish, including forward and reverse genetics and chemical screenings. Last, we review the models used to induce cardiac injury and essential ideas derived from studying natural regeneration. Studies using zebrafish have the potential to accelerate the discovery of new strategies to treat cardiac diseases.

中文翻译：

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心脏病的斑马鱼模型：从偶然突变到精准医学

心脏病是全世界死亡的主要原因。尽管进行了数十年的研究，但大多数心脏病的治疗方法有限，而且通常唯一的治疗方法是心脏移植。因此，迫切需要开发治疗心脏病的新治疗方法。再现人类病理生理学的动物模型对于揭示疾病生物学和发现疗法至关重要。传统上，哺乳动物被用作心脏病模型，但生成和维护新模型的成本过高，而且研究的通量非常低。在过去的十年中，斑马鱼已成为一种易于处理的心脏病模型，这归功于使这种动物受到发育生物学家欢迎的几个特征。斑马鱼的受精和发育是外部的；可以获得大量胚胎，价格便宜且易于维护，并且可以通过操作来创建新的遗传模型。此外，斑马鱼在受伤后表现出非凡的心脏再生能力。这篇综述总结了 25 年来使用斑马鱼研究心脏的研究，从经典的正向筛查到现代方法，以模拟在心脏病患者身上发现的突变。我们讨论了这种模式生物的优点和局限性，并介绍了在斑马鱼中使用的实验方法，包括正向和反向遗传学以及化学筛选。最后，我们回顾了用于诱发心脏损伤的模型和研究自然再生的基本思想。使用斑马鱼的研究有可能加速发现治疗心脏病的新策略。