Scientists discover genetic ‘secret switch’ that may ‘revolutionize’ heart attack treatment

SYDNEY, Australia — A new genetic discovery in fish may change post-heart attack treatments in humans for the better. Researchers from the Victor Chang Cardiac Research Institute have discovered a new gene that appears capable of assisting in the repair of damaged cardiac muscles after a heart attack.

Study authors say the credit for the findings go to the zebrafish. Scientists discovered a “genetic switch” in these tiny creatures that facilitates the division and multiplication of cells following heart attacks. In most cases, zebrafish make a full recovery after suffering a cardiac event. The small freshwater species have wide-ranging uses for science. Despite being a fish, they are extremely similar to humans on a molecular, genetic, and cellular level.

Zebrafish (Credit: Victor Chang Cardiac Research Institute)

The fact that zebrafish can heal their own hearts, therefore, does not come as a surprise to researchers. However, it’s been a mystery up until now how the species accomplishes that feat. The gene in question, Klf1, had previously only been found in red blood cells.

“Our research has identified a secret switch that allows heart muscle cells to divide and multiply after the heart is injured. 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,” explains study leader Dr. Kazu Kikuchi, in a media release. “With these tiny little fish sharing over 70% of human genes, this really has the potential to save many, many lives and lead to new drug developments.”

How does Klf1 make such a big cardiac difference?

The gene actually changes the metabolic wiring of uninjured cardiac muscle cells, making them “more immature.” These changes allow the uninjured cells to divide and produce new cells. When researchers removed Klf1 from a group of zebrafish, all the subjects lost their heart-healing abilities.

“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,” says Professor Bob Graham, Head of the Institute’s Molecular Cardiology and Biophysics Division. “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.”

Notably, Klf1 doesn’t appear to play any role in the early development of the heart. The team adds the gene only takes part in repairs and healing.

“This is clear evidence that the regeneration you get after a heart injury is not the same as what happens during the development of the heart but involves an entirely different pathway; an issue that has been debated for years,” Prof. Graham concludes.

The study appears in the journal Science.

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John Anderer

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