Zebrafish Cardiovascular Disease Models

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.

The zebrafish as a model to study human cardiovascular disease.

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)

GeneAssociated Human DiseaseZebrafish Genotype
APOOP1Lipid Associated-CardiomyopathyIncreased the LDL-C levels, increase in the average number of vascular plaques
GNG11, SYT10, RGS6, HCN4, NEO1, KIAA1755Heart Rate VariabilitySinoatrial pauses and arrests, cardiac edema and uncontrolled atrial contractions
HSPB7Dilated CardiomyopathyCardiomegaly, cardiac fibrosis and sarcomeric abnormalities
KCNH2Long QT SyndromeSevere repolarization
KCNIP1Atrial FibrillationHigh atrial rate
KIF20ACongenital CardiomyopathyRelative tachycardia, red blood cells proximal to the atrium and cardiac edema
LMCD1, TNS1Mitral Valve ProlapseIncreased atrioventricular regurgitation, moderate reduction in cardiac looping
NFATC1Atrioventricular Septal DefectAltered atrioventricular canal patterning and cardiac looping defects
PBX3Congenital Heart DefectsMyocardial morphogenesis defects
PLXND1Lipid Associated-CardiomyopathyModulate angiogenesis, reduced capacity to store lipid in visceral adipose tissue
PRRX1Atrial FibrillationAtrial 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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