Zebrafish Protein Repairs Heart Tissue – A Possible Heart Attack Therapy

Researchers at the Hubrecht Institute, University Medical Center (UMC) in Utrecht, The Netherlands, have isolated a protein that allows adult zebrafish to repair a damaged heart.

Heart attacks or myocardial infarctions cause massive losses of cardiomyocytes, our heart cells. The loss of these cells happens in the millions and once they die cannot be regenerated. In an adult zebrafish, however, a damaged heart can be regenerated.

Jeroen Bakkers who is in the Department of Pediatric Cardiology at UMC notes in a Hubrecht Institute news release:

“We don’t understand why some species can regenerate their hearts after injury while others cannot. 

He goes on.

“By studying zebrafish and comparing them to other species, we can uncover the mechanisms of heart regeneration. This could eventually lead to therapies to prevent heart failure in humans.”

What exactly does a zebrafish have that humans or laboratory mice do not? It is a protein that gets activated when a zebrafish’s heart is damaged. A gene by the name Hmga1 generates a protein with the same name that stimulates cardiomyocyte production when a heart muscle is injured. The injury appears to be the stimulus for the gene to express the protein.

The study’s results have been published in the January 2, 2025, issue of Nature Cardiovascular Research and in typical scientific jargon is described as follows:

“A correlation between Hmga1, an architectural non-histone protein, and regenerative capacity, as Hmga1 is required and sufficient to induce cardiomyocyte proliferation and required for heart regeneration.”

Translating to normal English, it means a gene-activated protein, Hmga1, causes heart muscle cells in mice that normally do not replicate to reproduce.

Dennis de Bakker, a study author describes the results of using the Hmga1 protein to regrow heart muscle cells in mice as “remarkable.”

Why?

Because the observed muscle cell regrowth in the presence of the protein has no adverse effects. There is no excessive growth or enlargement of the heart muscle.

Neither mice nor humans produce Hmga1 protein when a heart attack occurs even though the gene that expresses it is found in both animals. It just doesn’t activate if the heart muscle is damaged. That’s why researchers want to explore using the protein as a treatment to regenerate heart muscle cells after a heart attack. First, they are doing it with mice. Then they will use human heart muscle cells cultured in the laboratory and finally if successful will move to test the protein therapy in human clinical trials.

The little zebrafish that I used to breed in my home aquarium is today seen as a valuable resource for scientific research. That’s because zebrafish and humans share 70% of the same genes making the fish a good candidate for studying genetic diseases. The result is zebrafish research is looking to find cures for hemophilia, thyroid cancer, and some rare genetic conditions requiring one-off personalized medical treatments.

Since the dawn of modern medical research, scientists have relied on interspecies studies using animal surrogates. Zebrafish join a long lineage that includes mice, rats, dogs, monkeys, pigs, rabbits, sheep and even horses. But for how much longer?

Today, we are not far away from seeing two digital substitutes.

The first is the emergence of digital twins which are replicas of the real thing, whether it is a military jet or a human body. Testing on a digital twin to see results makes testing on an animal redundant.

The second is artificial intelligence (AI) which can be applied to analyze large datasets to identify new chemicals and drugs as well as genes and proteins to develop adaptive therapies.

These substitutes for animal surrogates are heartening as we, as a species, begin to better understand we aren’t the keepers of life on the planet but are more partners in this planet’s evolution. That doesn’t mean we won’t continue to study other species to learn about their unique attributes to help us better understand ourselves, cure diseases, deal with ageing, learn how to regrow lost limbs and organs or repair a broken heart.