5 ways zebrafish are helping us find a cure for heart disease

Zebra fish in the lab

The zebrafish has a special place in heart disease research. Here are some of the BHF-funded projects which use the fish to look for new treatments for heart failure and other heart conditions too.

1. Watching the zebrafish heart beat in 3D

The zebrafish embryo is transparent, which makes it ideal to study how the heart first starts to grow and beat. The development of its heart also begins in a similar way to humans.

Dr Jonathan Taylor and colleagues at the University of Glasgow have been awarded a grant to develop a bespoke microscope so they can study this process in minute detail. Using a specialised video camera attached to a microscope, they will collect and analyse images at different points in the heart cycle and use them to create a 3D movie image at different stages as the fish develops. 

This will allow them to study heart structure and function during early development, and to assess the effects of genetic changes, and potential new drugs, on heart development and growth in detail.

2. Improving drugs for irregular heart rhythms

When a heart beats irregularly, it can increase the risk of blood clots forming in the chambers of the heart, which in turn increases the risk of a stroke.

We’ve awarded a team of researchers at the University of Birmingham, led by Professor Attila Sik, £295,840 to try to find better drugs for irregular heart rhythms.

Unlike humans, zebrafish can repair their own hearts if they are damaged

Professor Sik’s technology involves placing a potential new drug into a small pool with a zebrafish embryo. By using a micro-electrocardiogram (ECG) – like a human ECG but on a microscopic scale - the scientists can monitor the effect of the drug on the zebrafish’s heartbeat, down to the tiniest detail. 

Thousands of drugs can be tested using thousands of zebrafish embryos. The zebrafish heartbeat has a very similar electrical profile to that of humans, so this technique is a good way to spot the potential effects on humans much more quickly than in human trials and without needing to test it on humans.

3. Looking at gene mutations

ZebrafishOur genes contain instructions for the body to create proteins – the molecules needed for our bodies’ tissues and functions to be created and to work properly. When a gene is mutated, the structure of proteins in the body can change, causing diseases.

Popeye domain-containing (Popdc) proteins are a family of proteins named after the cartoon character, because of the fact that they are particularly found in muscles of the body. Changes in these proteins have been linked with heart rhythm problems and muscular dystrophy, a group of genetic conditions.

We’ve awarded £296,341 to a team of researchers at Imperial College London, led by Professor Thomas Brand, to look at how changes in Popdc proteins in zebrafish hearts can lead to conditions such as heart rhythm disorders. 

With this knowledge, researchers hope to gain a better understanding of these genetic changes in humans with hopes of developing new treatments.

4. Studying how blood flow affects the growth of blood vessels

When blood vessels become damaged, cardiovascular conditions such as coronary heart disease or stroke can develop. Understanding how vessels form could help scientists find ways of growing new, healthy vessels for people with damaged vessels.

The University of Sheffield is known for its work on zebrafish and has the largest number of zebrafish heart researchers in the UK.

Unlike humans, zebrafish can repair their own hearts if they are damaged. By studying zebrafish, researchers hope they can find clues to repairing the human heart after damage.

Thousands of drugs can be tested using thousands of zebrafish embryos

We've awarded £208,054 to Dr Timothy Chico and colleagues at the University of Sheffield, to look at how new vessel growth is controlled and how blood flow affects this process. 

In particular, they are exploring how blood flow affects the activity of a protein called Notch, which is involved in processes such as helping the vessels sprout and grow in the right direction, and deciding which vessels are to be veins and which are to be arteries.

This could lead to new therapies targeting the Notch protein, which could help treat diseases caused by vessel damage.

We’ve also helped to fund a state of the art microscope for Dr Chico and his colleagues in Sheffield. The microscope will allow scientists to study how cells behave and work within the living zebrafish in much greater detail than they were able to achieve before.

5. Finding a cure for heart failure

People who survive a heart attack may have heart tissue damage that can lead to debilitating heart failure.

In humans, the heart cannot repair itself. But zebrafish can repair their hearts - heart muscle cells near the damaged area lose their muscle properties and revert back to stem cells, which can repair the heart tissue.

Scientists know that a protein called Mef2 is needed to turn zebrafish stem cells into heart muscle cells.

Dr Yaniv Hinits and colleagues believe that zebrafish muscle cells near wounds are able to turn Mef2 on and off – turning Mef2 off to turn the cells back to stem cells, then turning it back on so they can become heart muscle cells to repair the heart. We’ve given the team a grant to find out if controlling Mef 2 might hold the key to heart muscle repair in humans.

This research may reveal new ways to encourage our own hearts to recover better

We’re also funding Professor Roger Patient and BHF Professor Paul Riley at the University of Oxford to look at how zebrafish heart muscle cells in order to replace an area of damaged tissue with healthy cells. 

They are looking at how these dividing heart muscle cells are different to non-dividing cells. This research may reveal ways to trigger mouse and human heart muscle cells to divide - and may in the future hold the key to repairing human hearts.

And at the University of Bristol, Dr Rebecca Richardson has been awarded a BHF Research Fellowship worth £536,838 to look at how zebrafish can remove scar tissue that has formed at a site of heart muscle damage. 

She will work out which cells are involved in forming and remodelling the scar, before working out exactly how they do this, and which genes and associated signalling pathways are involved. 

This research may reveal new ways to encourage our own hearts to recover better, and even prevent scar tissue forming or remove it following a heart attack.

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