Zebrafish cardiovascular research: Assays and Examples

The zebrafish is a common alternative model in cardiovascular research due to its heart formation being similar to that of the human heart.

Cardiovascular disease is the main cause of death in the world, with 17.9 million people dying each year (World Health Organization), representing 32% of all deaths in the world.

There are several forms of heart disease, including coronary heart disease and cerebrovascular disease. Over four out of five deaths due to a coronary disorder are caused by a heart attack or a stroke, and a third of these take place in people under 70 years of age.

These data reveal the importance of finding a cure to treat heart diseases as soon as possible.

Why is zebrafish suitable to study human heart disease?

The zebrafish heart is very similar to a human heart, reason why it is a suitable model to study human heart diseases.

The human heart is made up of four chambers, two on the left and two on the right. When damage occurs to the heart (through cardiovascular disease or a heart attack) the cells in the heart are damaged and do not reproduce.

Although the zebrafish heart only contains two chambers, these are very similar to the human heart, making it a suitable model to study human heart disease.

The advantages of using the zebrafish for cardiac study include: 

• The heart regenerates if it is injured.
• The rapid development of the heart, starting beating 24 hours after fertilisation.
• Transparent embryo facilitating the study of the heart.
• Similar behaviour to the human heart.
• Blood circulation is not required in the first week of life.

General advantages of zebrafish for medical research include:

• Small and transparent, making it easy to study.
• Cheap to breed and house.
• Quick development.
• High breeding numbers – hundreds are reproduced at once.
• Easy to genetically engineer.

The development of the zebrafish heart

The heart is the first organ to form and function in the zebrafish and it develops in the same manner as in the human heart.

As the heart forms, it is possible to study and identify any defects that may form due to the transparency of the embryo. This allows researching one of the most common forms of birth defects in humans – congenital heart defects.

This model also makes it possible to study blood flow and the effects in the heart when it reduces.

Examples of heart disease assays using zebrafish

Zebrafish is used in many ways to study heart disease and to research new treatments, for example:

• To study irregular heart rhythms and to identify drugs for treatment. An irregular heart rhythm can cause a stroke as it causes blood to clot and block the heart chambers. A microscopic ECG monitor is used on zebrafish to study the effect of test drugs on the heartbeat.
• Monitoring heartbeat to study how the heart beats and grows when the embryo is formed. This is done in 3D and shows different stages of heart development and how drugs can affect it.
• Studying gene mutations to identify how they can occur in the human heart. Gene mutations cause changes in proteins that can result in heart rhythm problems. An understanding of how and why this occurs using zebrafish can help to develop new treatments.
• Curing heart failure due to a heart attack. After a heart attack, the heart cannot repair itself. If the person survives, the heart will not be fully functioning due to damaged scar tissue. The zebrafish heart can repair itself and research is been carried out to study whether damaged human heart tissue can be removed or improved after a heart attack.
• The study of blood flow and blood vessel formation. Understanding more about how the zebrafish heart can self-repair after being damaged can give an insight into how strokes and heart disease could be cured. Currently, the damage to these vessels due to heart disease is irreparable, but this could change in the future, thanks to the use of zebrafish.

The use of zebrafish in cardiovascular studies is an important part of pharmaceutical research and the sooner we can find cures and treatments for heart disease, the sooner the number of human deaths worldwide could be reduced. At Biobide we perform the cardiotoxicity assay that allows detecting cardiac arrhythmias in zebrafish larvae, that resembles QT prolongation effects in humans. This allows for selecting safer candidates without cardiotoxicities that can be life-threatening.

 Sources

1. https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.15473
2. https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1
3. https://www.bhf.org.uk/informationsupport/heart-matters-magazine/research/fish-research
4. https://pubmed.ncbi.nlm.nih.gov/27503203/ 
5. https://encyclopedia.pub/entry/7489