Zebrafish as a Unique Model to Study Cardiovascular Physiology and Disease

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 13262

Special Issue Editors


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Guest Editor
Department of Biomolecular Medicine, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium
Interests: zebrafish; cardiovascular physiology; disease models; drug screening; connective tissue; rare genetic disease; Marfan syndrome; nitric oxide; mouse models

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Guest Editor
Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Ludwigstrasse 43, 61231 Bad Nauheim, Germany
Interests: cardiovascular; cardiac valve; zebrafish; regeneration; calcification

Special Issue Information

Dear Colleagues,

Over the past few decades, zebrafish have come to the forefront as a powerful, versatile animal model for studying a range of physiological processes. Combining the latest genome editing and imaging technologies with the scalability of this vertebrate model allows scientists to approach biological questions from an unprecedented angle. The zebrafish model has already proved its merit for the study of cardiovascular physiology, disease and regeneration. It has helped us to better understand the development of the cardiovascular system as well as regenerative mechanisms and the roles of essential signaling pathways. In recent years, the rise of CRISPR/Cas9 and related genome-editing tools has allowed for the rapid generation of new, precise models of cardiovascular disease. Advanced imaging modalities have been instrumental in visualizing normal and aberrant processes in these models. Not only do these technologies encompass the in vivo and ex vivo microscopy of early developmental stages, but recently, the detailed phenotyping of adult zebrafish has also become possible by increasing the resolution of imaging techniques, which were previously only applicable to larger animal models. Another unique advantage of using zebrafish embryos or larvae as a model is the opportunity to perform in vivo, unbiased, high-throughput drug screening. Using this approach, new disease mechanisms can be discovered that would escape scrutiny using standard targeted approaches based on a priori knowledge.

This Special Issue aims to highlight the current state of the art of the applications of zebrafish models for cardiovascular research. The topics may include (but are not limited to) zebrafish models of cardiovascular disease and regeneration, insights into signaling mechanisms based on zebrafish studies, advances in phenotyping techniques, and drug-discovery efforts. Original articles as well as reviews highlighting the latest advances in the field are welcomed.

Prof. Dr. Patrick Y. Sips
Dr. Anabela Bensimon-Brito
Guest Editors

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Keywords

  • zebrafish
  • cardiovascular system
  • physiology
  • genome editing
  • drug discovery
  • cell signaling
  • development
  • regeneration
  • disease models
  • imaging techniques

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Published Papers (3 papers)

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Research

14 pages, 1687 KiB  
Article
The Effect of Hypothermia and Osmotic Shock on the Electrocardiogram of Adult Zebrafish
by Elodie Arel, Laura Rolland, Jérôme Thireau, Angelo Giovanni Torrente, Emilie Bechard, Jamie Bride, Chris Jopling, Marie Demion and Jean-Yves Le Guennec
Biology 2022, 11(4), 603; https://doi.org/10.3390/biology11040603 - 15 Apr 2022
Cited by 5 | Viewed by 2488
Abstract
The use of zebrafish to explore cardiac physiology has been widely adopted within the scientific community. Whether this animal model can be used to determine drug cardiac toxicity via electrocardiogram (ECG) analysis is still an ongoing question. Several reports indicate that the recording [...] Read more.
The use of zebrafish to explore cardiac physiology has been widely adopted within the scientific community. Whether this animal model can be used to determine drug cardiac toxicity via electrocardiogram (ECG) analysis is still an ongoing question. Several reports indicate that the recording configuration severely affects the ECG waveforms and its derived-parameters, emphasizing the need for improved characterization. To address this problem, we recorded ECGs from adult zebrafish hearts in three different configurations (unexposed heart, exposed heart, and extracted heart) to identify the most reliable method to explore ECG recordings at baseline and in response to commonly used clinical therapies. We found that the exposed heart configuration provided the most reliable and reproducible ECG recordings of waveforms and intervals. We were unable to determine T wave morphology in unexposed hearts. In extracted hearts, ECG intervals were lengthened and P waves were unstable. However, in the exposed heart configuration, we were able to reliably record ECGs and subsequently establish the QT-RR relationship (Holzgrefe correction) in response to changes in heart rate. Full article
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15 pages, 5984 KiB  
Article
Precise Dose of Folic Acid Supplementation Is Essential for Embryonic Heart Development in Zebrafish
by Xuhui Han, Bingqi Wang, Dongxu Jin, Kuang Liu, Hongjie Wang, Liangbiao Chen and Yao Zu
Biology 2022, 11(1), 28; https://doi.org/10.3390/biology11010028 - 26 Dec 2021
Cited by 11 | Viewed by 5658
Abstract
Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac [...] Read more.
Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. Moreover, we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid and mthfr−/− mutant all gave rise to early pericardial edema and cardiac defect at 3 days post fertilization (dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5 dpf. The expression levels of cardiac marker genes hand2, gata4, and nppa changed in the abnormality of folate metabolism embryos and mthfr−/− mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. Furthermore, our results reveal that folic acid has a dose-dependent effect on early cardiac development. Precise dosage of folic acid supplementation is crucial for the embryonic development of organisms. Full article
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15 pages, 3116 KiB  
Article
Zebrafish Model to Study Angiotensin II-Mediated Pathophysiology
by Bhagyashri Joshi, Ganesh Wagh, Harmandeep Kaur and Chinmoy Patra
Biology 2021, 10(11), 1177; https://doi.org/10.3390/biology10111177 - 13 Nov 2021
Cited by 5 | Viewed by 3818
Abstract
Hypertension, a common chronic condition, may damage multiple organs, including the kidney, heart, and brain. Thus, it is essential to understand the pathology upon ectopic activation of the molecular pathways involved in mammalian hypertension to develop strategies to manage hypertension. Animal models play [...] Read more.
Hypertension, a common chronic condition, may damage multiple organs, including the kidney, heart, and brain. Thus, it is essential to understand the pathology upon ectopic activation of the molecular pathways involved in mammalian hypertension to develop strategies to manage hypertension. Animal models play a crucial role in unraveling the disease pathophysiology by allowing incisive experimental procedures impossible in humans. Zebrafish, a small freshwater fish, have emerged as an important model system to study human diseases. The primary effector, Angiotensin II of the RAS pathway, regulates hemodynamic pressure overload mediated cardiovascular pathogenesis in mammals. There are various established mammalian models available to study pathophysiology in Angiotensin II-induced hypertension. Here, we have developed a zebrafish model to study pathogenesis by Angiotensin II. We find that intradermal Angiotensin II injection every 12 h can induce cardiac remodeling in seven days. We show that Angiotensin II injection in adult zebrafish causes cardiomyocyte hypertrophy and enhances cardiac cell proliferation. In addition, Angiotensin II induces ECM protein-coding gene expression and fibrosis in the cardiac ventricles. Thus, this study can conclude that Angiotensin II injection in zebrafish has similar implications as mammals, and zebrafish can be a model to study pathophysiology associated with AngII-RAS signaling. Full article
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