Abstract
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 in vivo 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.
Highlights
Heart disease is the number one cause of mortality and years of life lost globally (GBD 2016 Causes of Death Collaborators, 2017)
Transgenic cmlc1 mutant adult zebrafish hearts display disrupted sarcomeric structure, atrial enlargement, and electrical abnormalities associated with human Atrial fibrillation (AF) (Orr et al, 2016). These findings describe the cause of a rare subtype of AF due to a primary, atrial-specific sarcomeric defect. dcos226 embryonic zebrafish mutants, identified from an ENU mutagenesis screen, develop Heart failure (HF) due to interrupted morphogenesis following uncoordinated ventricular contraction, as investigated with optical mapping/calcium imaging (Chi et al, 2010). dco encodes the gap junction protein Gja3/Cx46
Almost half of HF patients suffer sudden cardiac death (SCD) mainly due to ventricular tachyarrhythmias, putting SCD on par with failure of pump function as a cause of mortality in HF (Tomaselli et al, 1994). It follows that a better understanding of zebrafish cardiac electrophysiology and its limitations is needed for relevant modeling of human cardiac electrophysiology and arrhythmias associated with HF
Summary
Heart disease is the number one cause of mortality and years of life lost globally (GBD 2016 Causes of Death Collaborators, 2017). We first briefly review early developmental mutants discovered in forward genetic mutagenesis screens, as they demonstrated the value of investigating cardiac phenotypes in embryonic zebrafish, and paved way for the increasing number of studies using reverse genetic techniques for modeling cardiovascular disease in zebrafish. The absence of titin results in failure of sarcomeric assembly (Xu et al, 2002) These first models, identified from forward genetic mutagenesis screens, demonstrated the value of embryonic zebrafish developing without functional circulation for the study of severe cardiac phenotypes. Knockdown of pkd with morpholinos in embryonic zebrafish results in reduced cardiac contractile function and atrioventricular block due to impaired cardiomyocyte calcium cycling (Paavola et al, 2013). Hypertrophy Hyperplasia Hypertrophy, cardiac dysfunction Cardiac dysfunction, AV-block left-right asymmetry Cardiac dysfunction Cardiac dysfunction Cardiac dysfunction
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
