Zebrafish as a Model for Cardiovascular and Metabolic Disease: The Future of Precision Medicine

Abstract

The zebrafish (Danio rerio) has emerged as an appreciated and versatile model organism for studying cardiovascular and metabolic diseases, offering unique advantages for both basic research and drug discovery. The genetic conservation between zebrafish and humans and their high fecundity and transparent embryos allow for efficient large-scale genetic and drug-oriented screening studies. Zebrafish possess a simplified cardiovascular system that shares similarities with mammals, making them particularly suitable for modeling various aspects of heart development, function, and disease. The transparency of zebrafish embryos enables the real-time visualization of cardiovascular dynamics, offering insights into early embryonic events and facilitating the study of heart-related anomalies. In metabolic research, zebrafish provide a cost-effective platform for modeling obesity, type 2 diabetes, hyperlipidemia, and other metabolic disorders. Their high reproductive rate allows for the generation of large cohorts for robust statistical analyses, while advanced genetic tools, such as CRISPR/Cas9, enable precise gene editing with which to model specific genetic mutations associated with human diseases. Zebrafish metabolic models have been instrumental in elucidating the molecular mechanisms underlying metabolic diseases, studying the effects of environmental factors, and identifying potential therapeutic targets. Additionally, the permeability of zebrafish embryos to small molecules facilitates drug discovery and screening, offering a rapid and economical approach to identifying compounds with therapeutic potential. In conclusion, zebrafish cardiovascular and metabolic disease models continue to contribute significantly to our perception of disease pathogenesis, providing a platform for translational research and developing novel therapeutic interventions. The versatility, scalability, and genetic manipulability of zebrafish position them as an invaluable asset in unraveling the complexities of cardiovascular and metabolic diseases. This review presents an overview of the zebrafish model's key features and contributions to investigating cardiovascular and metabolic disorders. We discuss the benefits and drawbacks of using zebrafish models to study human disease and the critical findings revealed by the progress in this endeavor to date.

Keywords: CRISPR; TALEN; cardiovascular disease; gene editing; metabolic disease; transgenesis; zebrafish.

Figure 1

Outline showing various applications of zebrafish in the field of cardiovascular disease and metabolic disease.

Figure 2

Adult zebrafish electrocardiogram (A) Electrocardiogram recordings of wild-type (bh^+/+) zebrafish. X-axis represents time in milliseconds (ms), and Y-axis represents voltage in millivolts (mV). (B) Graph showing an overlay of wild type and bh^-/- mutant ECG recordings (Regular line and dashed line represents the ECG profiles of wild type and bh^-/- fish, respectively). P, Q, R, S & T represent regular ECG waves. The image in the figure were adapted from the author’s publication [119].