Teaching the heart to grow again

Within the first week after birth, hearts can repair themselves without scarring. A group of scientists, including two at OMRF, are looking for a way to restore that ability later in life, when scarring can lead to abnormal heart function.

OMRF researchers Luke Szweda, Ph.D., and Mike Kinter, Ph.D., in collaboration with University of Texas Southwestern Medical Center scientist Hashem Sadek, M.D., Ph.D., found that oxygen is the switch that turns off heart regeneration. Their work was published in the journal Cell.

“Using mice, Dr. Sadek found that you could clip off a small piece of the heart or deprive it of oxygen in the first four days after birth, and the heart would completely repair itself without fibrosis or scarring,” said Szweda, who holds the Hille Family Foundation Chair in Neurodegenerative Disease Research at OMRF. “Older hearts can make some repairs, but that causes scarring, which disrupts the optimal function of the heart.”

That’s because heart cells are still rapidly dividing within the first week after birth, he said. After about seven days, the heart cells stop dividing and start growing in size, in a process called cell cycle arrest.

“Essentially, the heart decides it is more important to power the circulation of blood than to continue dividing,” Szweda said. “That requires more energy, so heart cells rev up their power plants, called the mitochondria, which burn oxygen for fuel.”

Some of the oxygen isn’t completely consumed, and leaves behind “free radicals,” which cause minor damage to the cells’ DNA—prompting the cells to stop dividing.

“When cells with damaged DNA divide, the cells they make may have altered function that is detrimental to the heart,” Szweda said. “That might explain why free radicals are used to signal an end to growth by division.”

Using an antioxidant called catalase to capture the free radicals produced by the mitochondria, however, allowed researchers to extend the regenerative period of the hearts up to another two weeks, he said.

“Knowing the key mechanism that turns the heart’s regenerative capacity off in newborns tells us how we might discover methods to reawaken that capacity in the adult mammalian heart,” said Sadek.

The heart is an elegant machine, Szweda said. If some of the muscle is replaced with scar tissue after an injury, it disrupts the architecture and can lead to serious health problems.

The research opens up new possibilities for therapeutics if scientists can find a way to restore the heart’s regenerative abilities, he said. At OMRF, scientists are trying to understand precisely how free radicals are used to communicate and how the heart cells receive the message to stop dividing.

Funding for OMRF’s research was provided by grant no. 1R01 AG-16339 from the National Institute on Aging, a part of the National Institutes of Health.