Narumanchi Suneeta, Wang Hong, Perttunen Sanni, Tikkanen Ilkka, Lakkisto Päivi, Paavola Jere
Unit of Cardiovascular Research, Minerva Foundation Institute for Medical Research, Biomedicum Helsinki, Helsinki, Finland.
Abdominal Center Nephrology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Front Cell Dev Biol. 2021 May 20;9:662583. doi: 10.3389/fcell.2021.662583. eCollection 2021.
Heart failure causes significant morbidity and mortality worldwide. The understanding of heart failure pathomechanisms and options for treatment remain incomplete. Zebrafish has proven useful for modeling human heart diseases due to similarity of zebrafish and mammalian hearts, fast easily tractable development, and readily available genetic methods. Embryonic cardiac development is rapid and cardiac function is easy to observe and quantify. Reverse genetics, by using morpholinos and CRISPR-Cas9 to modulate gene function, make zebrafish a primary animal model for studies of candidate genes. Zebrafish are able to effectively regenerate their hearts following injury. However, less attention has been given to using zebrafish models to increase understanding of heart failure and cardiac remodeling, including cardiac hypertrophy and hyperplasia. Here we discuss using zebrafish to study heart failure and cardiac remodeling, and review zebrafish genetic, drug-induced and other heart failure models, discussing the advantages and weaknesses of using zebrafish to model human heart disease. Using zebrafish models will lead to insights on the pathomechanisms of heart failure, with the aim to ultimately provide novel therapies for the prevention and treatment of heart failure.
心力衰竭在全球范围内导致了严重的发病率和死亡率。目前，对于心力衰竭发病机制的理解以及治疗方案仍不完整。由于斑马鱼与哺乳动物心脏具有相似性、发育快速且易于操作、基因方法易于获取，已证明斑马鱼在人类心脏病建模中十分有用。胚胎心脏发育迅速，心脏功能易于观察和量化。通过使用吗啉代寡核苷酸和CRISPR-Cas9来调节基因功能的反向遗传学方法，使斑马鱼成为研究候选基因的主要动物模型。斑马鱼在心脏受伤后能够有效地进行心脏再生。然而，利用斑马鱼模型来增进对心力衰竭和心脏重塑（包括心肌肥大和增生）的理解却较少受到关注。在此，我们讨论利用斑马鱼来研究心力衰竭和心脏重塑，并综述斑马鱼基因、药物诱导及其他心力衰竭模型，探讨使用斑马鱼对人类心脏病进行建模的优缺点。使用斑马鱼模型将有助于深入了解心力衰竭的发病机制，最终目标是为心力衰竭的预防和治疗提供新的疗法。
