Zebrafish Cardiovascular Disease Models

The zebrafish has emerged as an important vertebrate model for cardiovascular disease study. Zebrafish larvae are transparent, allowing visualization of the heart and vasculature for high-throughput phenotypic assays. In particular, the formation of the heart chambers, cardiac contraction, vessels, and blood flow are easily observed in vivo. Besides, during the first days of development, zebrafish embryos are not fully dependent on a functional cardiovascular system, since they get sufficient oxygen by passive diffusion. Thus, embryos with severe cardiovascular defects survive throughout embryogenesis facilitating the phenotypic analysis of mutations that in mammals could cause early embryonic lethality. As a result, severe phenotypes concerning cardiac valve development could be studied even in the absence of blood circulation, resulting in the notion that intracardiac flow dynamics affect the morphogenesis of valve development. Moreover, the zebrafish embryonic heart rate is beats per minute, much closer to the human heart rate than the mouse.

Figure 1. The zebrafish as a model to study human cardiovascular disease. (Asnani A, Peterson R T. 2014)

Besides, the efforts that had been made out of the combination of population-based genome-wide association studies (GWAS) and functional analysis in zebrafish models reveal uncharacterized mechanisms that give the knowledge to design new prognostic and therapeutic strategies.

Table 1. An indicative table of GWAS-derived cardiomyopathy related genes studied in zebrafish. (Giardoglou P, Beis D. 2019)

Gene	Associated Human Disease	Zebrafish Genotype
APOOP1	Lipid Associated-Cardiomyopathy	Increased the LDL-C levels, increase in the average number of vascular plaques
GNG11, SYT10, RGS6, HCN4, NEO1, KIAA1755	Heart Rate Variability	Sinoatrial pauses and arrests, cardiac edema and uncontrolled atrial contractions
HSPB7	Dilated Cardiomyopathy	Cardiomegaly, cardiac fibrosis and sarcomeric abnormalities
KCNH2	Long QT Syndrome	Severe repolarization
KCNIP1	Atrial Fibrillation	High atrial rate
KIF20A	Congenital Cardiomyopathy	Relative tachycardia, red blood cells proximal to the atrium and cardiac edema
LMCD1, TNS1	Mitral Valve Prolapse	Increased atrioventricular regurgitation, moderate reduction in cardiac looping
NFATC1	Atrioventricular Septal Defect	Altered atrioventricular canal patterning and cardiac looping defects
PBX3	Congenital Heart Defects	Myocardial morphogenesis defects
PLXND1	Lipid Associated-Cardiomyopathy	Modulate angiogenesis, reduced capacity to store lipid in visceral adipose tissue
PRRX1	Atrial Fibrillation	Atrial action potential duration

Also, a broad range of standard cardiovascular drugs for humans used in daily clinical practice has analogous effects on zebrafish heart and vessels emphasizing the usage of the zebrafish as an important animal model in cardiovascular research.

Our Zebrafish Cardiovascular Disease Models

Creative Biogene has long-standing experience in conducting preclinical zebrafish model studies of cardiovascular disease. We offer consultancy and preclinical zebrafish models of cardiovascular disease including hypertension, arrhythmia, heart failure and atherosclerosis, etc. Similar to other animal models, wild-type zebrafish do not spontaneously develop cardiovascular diseases mimicking the human's conditions. Therefore, most of the current models rely on chemical interventions or genetic modifications.

Heart development and regeneration, and zebrafish cardiac models
Vascular development and zebrafish model for angiogenesis
Cerebrovascular development and cerebrovascular models
Zebrafish atherosclerosis models
Zebrafish hypercholesterolemic models
Zebrafish heart failure models
Zebrafish congenital heart defects models
Zebrafish hypertrophic and dilated cardiomyopathy models
Zebrafish arrhythmias models

Advantages

Easily monitoring the development and function of the heart and vasculature
Large-scale mutagenesis
Transgenic models available
High-throughput genetic and drug screening

Creative Biogene has an extensive portfolio of cardiovascular services by our zebrafish platform ranging from standard cardiovascular telemetry studies for safety assessment to pathophysiological models for specific therapeutic areas. Please contact us to explore what we can do for you!

References

Giardoglou P, Beis D. On zebrafish disease models and matters of the heart. Biomedicines, 2019, 7(1): 15.
Gut P, et al. Little fish, big data: zebrafish as a model for cardiovascular and metabolic disease. Physiological reviews, 2017, 97(3): 889-938.
Asnani A, Peterson R T. The zebrafish as a tool to identify novel therapies for human cardiovascular disease. Disease models & mechanisms, 2014, 7(7): 763-767.
Seto S W, et al. Zebrafish models of cardiovascular diseases and their applications in herbal medicine research. European journal of pharmacology, 2015, 768: 77-86.
Pott A, et al. Streamlining drug discovery assays for cardiovascular disease using zebrafish. Expert Opinion on Drug Discovery, 2020, 15(1): 27-37.
Wilkinson R N, et al. Zebrafish as a model of cardiac disease. Progress in molecular biology and translational science. Academic Press, 2014, 124: 65-91.
Bournele D, Beis D. Zebrafish models of cardiovascular disease. Heart failure reviews, 2016, 21(6): 803-813.

For research use only. Not intended for any clinical use.

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