Heart attacks are dangerous not just because of the initial event, but the long-term damage afterwards. Now scientists have discovered a dormant gene that could be reactivated to regenerate heart tissue, preventing the progression to heart failure.
After a heart attack, scar tissue often forms to allow the organ to keep its shape, but the downside is that this tissue doesn’t beat. Over time, that can lead to irregularities in the rhythm, which can progress to further heart attacks and eventually heart failure.
But not all animals have this weakness – zebrafish, for example, can repair damaged heart tissue like it was a skin-deep scratch. They can fully restore their heart function in as little as 60 days after an injury, which would be a nice superpower to have.
In a new study, scientists at the Hubrecht Institute in the Netherlands have discovered a protein that drives this heart tissue repair in zebrafish. They then applied it to mouse hearts, which also can’t regenerate, and found that it still works to repair damage there too, suggesting a pathway to a potential treatment in humans.
“We looked at the activity of genes in damaged and healthy parts of the heart,” said Dennis de Bakkers, first author of the study. “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.”
To see if those regenerative abilities were transferrable, the team used a virus vector to deliver Hmga1 to damaged tissue in the hearts of live mice. And sure enough, their heart muscle cells began to divide and grow, which significantly improved the heart function of the animals.
“There were no adverse effects, such as excessive growth or an enlarged heart,” said Mara Bouwman, co-first author of the study. “We also didn’t see any cell division in healthy heart tissue. This suggests that the damage itself sends a signal to activate the process.”
Of course, as with any mouse study there’s no guarantee that the results will carry across to humans. But there is a glimmer of hope in this case – the gene that codes for Hmga1 is still present in humans. It’s active during embryonic development but switches off soon after birth, so reactivating this dormant gene could help repair damage after a heart attack.
The team says that the next step of the research is to test whether the Hmga1 protein has the same effect on human heart muscle cells in culture.
The research was published in the journal Nature Cardiovascular Research.
Source: Hubrecht Institute
