Australian scientists discover ‘secret switch’ for the heart to heal itself

By John Elder

Cut off a piece of a zebrafish heart, and the little creature won’t be at the top of its game for a few days.

But after a month, the heart will grow back to normal and life goes on as normal.

Given that a heart attack in humans – known as a myocardial infarction – is akin to losing a piece of your heart (because tissue dies), scientists for years have been trying to understand how zebrafish heal themselves, with a view to replicating the process in people.

Now, scientists at the Victor Chang Cardiac Research Institute have identified the “genetic switch” in zebrafish that prompts heart cells to divide and multiply after a heart attack, “resulting in the complete regeneration and healing of damaged heart muscle in these fish”.

The gene switches off when the heart is fully healed

Dr Kazu Kikuchi, who led the research, published in Science on Friday, said he was “astonished” by the findings.

“Our research has identified a secret switch that allows heart muscle cells to divide and multiply after the heart is injured,” Dr Kikuchi said in a statement.

“It kicks in when needed and turns off when the heart is fully healed. In humans where damaged and scarred heart muscle cannot replace itself, this could be a game changer.”

So how might it work?

The researchers investigated a critical gene known as Klf1, which previously had only been identified in red blood cells.

They discovered Klf1 plays a vital role in healing damaged hearts.

The gene works by making uninjured heart muscle cells – called cardiomyocytes – more immature and changing their metabolic wiring, a process called dedifferentiation.

This allows them to divide and make new cells

So … what are cardiomyocytes?

Cardiomyocytes are the heart cells primarily involved in the contractile function of the heart that enables the pumping of blood around the body.

Ordinarily, adult mammalian hearts have a limited ability to generate new cardiomyocytes – whereas zebrafish will keep making new cells until their hearts are completely healed.

Dr Kazu Kikuchi discovered the switch that causes heart cells to heal themselves.

It’s been known for more than a decade that cardiomyocytes become more youthful in order to regenerate – and Dr Kikuchi was one of the researchers to demonstrate this.

What wasn’t known was how this was made to happen.

“Our new paper suggests it is Klf1 which triggers this,” Dr Kikuchi said.

This isn’t the same as stem cell technology

This isn’t the same as stem cell technology. In fact, dedifferentiating cardiomyocytes has proved to be a more effective healing process than stem cells.

It all comes down to that genetic switch.

Dr Kikuchi said that when the gene was removed, “the zebrafish heart lost its ability to repair itself after an injury such as a heart attack, which pinpointed it as a crucial self-healing tool”.

‘An incredible discovery’

Professor Bob Graham, head of the Institute’s Molecular Cardiology and Biophysics Division, says “this world-first discovery” – made in collaboration with the Garvan Institute of Medical Research – may well transform the treatment of heart attack patients and other heart diseases.

“The team has been able to find this vitally important protein that swings into action after an event like a heart attack and supercharges the cells to heal damaged heart muscle. It’s an incredible discovery,” Professor Graham said.

“The gene may also act as a switch in human hearts. We are now hoping further research into its function may provide us with a clue to turn on regeneration in human hearts, to improve their ability to pump blood around the body.”

Importantly, the team also found the Klf1 gene “played no role in the early development of the heart and that its regenerative properties were only switched on after a heart injury”.