Zebrafish can heal their damaged hearts. Humans hearts retain scars of earlier injuries.
In a new article published in the journal Science, titled “Krüppel-like factor 1 is a core cardiomyogenic trigger in zebrafish,” scientists from the Victor Chang Cardiac Research Institute in Sydney report finding a new genetic switch that could help damaged human heart muscles repair after a cardiac arrest.
Kazu Kikuchi, PhD, who led this research, says, “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. 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.”
When turned on this genetic switch in zebrafish allows heart muscle cells (cardiomyocytes) to multiply after a heart attack, resulting in the complete regeneration and repair of damaged heart muscles. The study finds a new role in heart regeneration for the gene Klf1, earlier identified as a factor important in red blood cell development. Klf1 can make uninjured heart muscle cells more immature and change their metabolic wiring. This allows them to divide and make new cells. When Klf1 is not present, the zebrafish heart cannot repair itself after an injury such as a heart attack, which demonstrates its crucial role in healing.
The team also found Klf1 plays no role in the early development of the heart and that its regenerative properties were only switched on after a heart injury. This indicates that regeneration after a heart injury is not the same as development of the heart.
“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.”
Graham says they hope to utilize this pioneering discovery, made in collaboration with the Garvan Institute of Medical Research, to transform the treatment of heart attack patients and other heart diseases.