• Scientists transplanted macrophages into hearts of mice and zebrafish
• Macrophages known to remove dead and dying cells from the body
• But macrophages also helped to create collagen and boost scar tissue
• Findings could lead to ways of improving repair after a heart attack 

Scientists are one step closer to understanding how fish can repair their own heart, offering clues for treatment in millions of heart attack patients. 

Zebrafish, a Mexican fish, are often the focus of scientific research because they are known to remarkably regenerate their own heart tissue.

University of Oxford scientists were ‘surprised’ to find that immune cells, called macrophages, were involved in the process.

For the first time, they were able to show the macrophages produce proteins called collagen which spur on recovery.  

The British Heart Foundation, which funded the research, said the discovery could ‘lead to new ways to enhance the repair after an attack’. 

Zebrafish, a Mexican fish, are often the focus of scientific research because they are known to remarkably regenerate their own heart tissue.  University of Oxford scientists were ‘surprised’ to find that immune cells, called macrophages, were involved in the process

People suffering from heart failure can’t regenerate their damaged hearts, and often the only cure is a heart transplant. 

Figures suggest there are 200,000 hospital visits in the UK each year because of heart attacks, which are known as a myocardial infarction with a further 800,000 in the US.

An attack occurs when the supply of blood to the heart is suddenly blocked, causing symptoms of chest pain, shortness of breath and feeling weak and anxious.

After someone has a heart attack, billions of cardiac muscle cells are lost and cannot be replenished.

The human body repairs the organ by forming a thick, permanent scar, which can make it more difficult for the heart to pump blood around the body. The organ could ultimately fail.

Professor Paul Riley and his team have been striving to understand how other animals’ hearts regenerate so well. 

Their latest study was on ‘zebrafish’, called tetra fish, and newborn mice which can regenerate its heart up to seven days after being born.

Both animals are believed to have more malleable, temporary scars, allowing their hearts to fully recover quicker and for blood to flow properly again. 

The team focused on how macrophages, a cell in the body involved in removing dead and dying cells, may contribute to these flexible scars.

They extracted macrophages from each animal to examine their gene expression. 

In both mice and fish, they found that macrophages were directly involved in the creation of the molecules that form part of a scar in the heart, particularly collagen.

The team said the research challenged the ‘dogma’ that only cells known as myofibroblasts are involved in creating the scar. 

Next, the team transplanted the cells into the hearts of both mice and a species of fish with injured hearts.

Next, the team transplanted the cells into the hearts of both mice and a species of fish with injured hearts.

They dyed collagen protein in the heart green to track how the scar developed.

Three weeks later, Professor Riley and his team were ‘very surprised’ to find part of the scars were green, indicating that macrophages help to boost collagen and form scar tissue.

Lead researcher Dr Filipa Simões said: ‘We have identified a new evolutionary conserved role for macrophages that is really challenging the current dogma that myofibroblasts are the sole cells contributing to the cardiac scar, that we believe could also be applied to the human heart.’

Although macrophages have been identified as playing a role in heart repair, it is not entirely clear how yet.

Before human clinical trials, the team need to do more research to understand the mechanism by which macrophages can contribute to the scar.

Dr Simões continued: ‘To effectively repair the heart, broadly speaking you need two things: one, you need to modulate the permanent scar into a transient scar and two, you need to replenish all the heart muscle cells and blood vessels that have been lost through injury.

‘Our study helps to address the first part of the problem as we identified macrophages as a new player in depositing the scar.’

Professor Jeremy Pearson, of the British Heart Foundation, said: ‘Our hearts struggle to repair themselves following the damage caused from a heart attack.

‘This can lead to heart failure, an incurable condition with worse survival rates than many cancers. We urgently need to find ways to repair the heart when it’s damaged.

‘Macrophages are an important part of our immune system, removing dead and dying cells and helping to repair damaged tissue.

‘By showing that macrophages produce collagen, a key part of scar tissue, this research could lead to new ways to enhance repair after a heart attack.’

The research was published in the journal Nature Communications.

HOW HAVE FISH BEEN USED IN HEART STUDIES BEFORE?
The zebrafish has been studied by The British Heart Foundation before. They have given funding for the following:

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. Scientists at the University of Glasgow are using a bespoke microscope to create a 3D movie image at different stages as the fish develops.
Researchers at the University of Birmingham are trying to find better drugs for irregular heart rhythms, which can increase the risk of blood a stroke. Thousands of drugs can be tested in detail on zebrafish embryos because they have a very similar electrical profile to that of humans.
Changes in a protein called Popdc have been linked with heart rhythm problems and muscular dystrophy, a group of genetic conditions. Imperial College London’s research into how changes in Popdc proteins in zebrafish hearts can lead to conditions such as heart rhythm disorders, holds hope for humans.
When blood vessels become damaged, cardiovascular conditions such as coronary heart disease or stroke can develop. The University of Sheffield has the largest number of zebrafish heart researchers in the UK. Here, they are looking at how zebrafish grow new vessels, which could help humans do the same once theirs is damaged.
People who survive a heart attack may have heart tissue damage that can lead to debilitating heart failure. Scientists across the UK are looking at how zebrafish turn stem cells into heart muscle cells, remove scar tissue and repair their hearts.
Source: British Heart Foundation

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