How are zebrafishes able to repair damaged hearts?

Unlike humans, zebrafish grow new heart muscle cells: they have a regenerative capacity. When a zebrafish heart is damaged, it can fully restore its function within 60 days. Researchers have now successfully discovered that the protein Hmga1 plays a key role in heart regeneration in zebrafish. The Hmga1 gene is present in mice and humans too, and the Hmga1 protein is important during embryonic development when cells need to grow a lot. However, after embryonic development, the gene for this protein is turned off in mice and humans. The researchers discovered that Hmga1 in zebrafish removes molecular ‘roadblocks’ on chromatin, which is the structure that packages DNA. When it is tightly packed, genes are inactive. When it unpacks, genes can become active again. The Hmga1 protein clears the way allowing dormant genes to get back to work. While in human hearts, as in adult mice, the gene for the Hmga1 protein is not active after a heart attack, in zebrafish the gene for the Hmga1 protein is active during heart regeneration.

The researchers tested if the protein works similarly in mammals. They applied the Hmga1 protein locally to damaged mouse hearts and found that the Hmga1 protein stimulated heart muscle cells to divide and grow, significantly improving heart function. Surprisingly, cell division occurred only in the damaged area, precisely where repair was needed. There were no adverse effects, such as excessive growth or an enlarged heart.