HQ Team
January 27, 2025: Researchers at the Hubrecht Institute have discovered that a protein can restore a damaged heart by activating dormant repair genes without causing side effects. This study could be a step forward in regenerative therapies for people who have suffered cardiovascular events.
The study, supported by the Dutch Heart Foundation and Hartekind Foundation, found that the protein Hmga1 plays a key role in heart regeneration in zebrafish. Furthermore, they found that in mice, this protein restores the heart by activating dormant repair genes.
Gene regeneration
After a heart attack, the human heart loses millions of muscle cells that cannot regrow. This often leads to heart failure, where the heart struggles to pump blood effectively. The study researchers found that, unlike humans, a zebrafish can regenerate a fully functional heart following damage within 60 days.
“We compared the zebrafish heart to the mouse heart, which, like the human heart, cannot regenerate,” says Dennis de Bakker, the study’s first author. “We looked at the activity of genes in damaged and healthy parts of the heart,” he explains. “Our findings revealed that the gene for the Hmga1 protein is active during heart regeneration in zebrafish but not in mice. This showed us that Hmga1 plays a key role in heart repair.” The Hmga1 protein is active during the embryonic development of cells. However, in adult cells, the gene for this protein is turned off.
During investigations, the researchers found that Hmga1 plays a role in unpackaging chromatin. It is the structure that surrounds the DNA into a tight package, which renders it inactive. When this chromatin is unravelled, the genes can become active again. “Hmga1 clears the way, so to say, allowing dormant genes to get back to work,” explains Mara Bouwman, co-first author.
Fish to mammals
When this discovery was taken further to test on mice with damaged hearts, the Hmga1 protein was able to stimulate the heart muscle cells to grow. Moreover, the division and regeneration of cells happened only in the damaged areas of the muscles. The benefit was that there were no side effects, such as an enlarged heart or muscles. Bouwman emphasizes, “This suggests that the damage itself sends a signal to activate the process.”
The scientists then compared the Hmga1 activity in zebrafish, mice, and human hearts. The Hmga1 protein is inactive in humans, though as in mice it is present during a cell’s embryonic development. “This provides a foundation for gene therapies that could unlock the heart’s regenerative potential in humans,” Bakkers explains.
Similar studies
Researchers from the University of North Carolina have found a way to transform scar tissue cells (fibroblasts) into healthy heart muscle cells (cardiomyocytes) with the help of a protein. A gene activity-regulating protein named Ascl1 is the catalyst in turning the action of fibroblasts into neurons.
These findings can help in targeted regenerative therapies, but the scientists say they need to refine and further test the methods before they are brought into clinical settings.
The findings were published in Nature Cardiovascular Research on January 2, 2025
