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Research Breakthrough May Help Heal Broken Hearts

UT Southwestern's Hesham Sadek (background) and study co-authors Wataru Kimura (left) and Bao Puente

Humans are exceptional in many ways, but some fish and lizards hold at least one distinct advantage over us: they can regrow their own hearts.

In 2011, a group of researchers at Dallas’ UT Southwestern Medical Center made the surprising discovery that mammals, too, can repair their own hearts. Unfortunately, they lose that ability shortly after birth. Now the same group of scientists has found that oxygen plays a key role in shutting off those regenerative capabilities. Their research, published recently in the journal Cell, may lead to improved treatments for heart failure in adults and heart defects in newborns.

The heart uses more oxygen than any other organ– about 30 percent of a person’s total supply. It needs that oxygen to generate enough energy to pump blood throughout the body. But as heart cells devour oxygen, they release byproducts that damage DNA and stop heart muscle cells from dividing and growing. “This is the price the heart pays to be energy efficient,” says Hesham Sadek, an assistant professor of internal medicine at UT Southwestern and the paper’s senior author.

In the womb, the heart receives a relatively low amount of oxygen. This led Sadek and his colleagues to hypothesize that the transition from an oxygen-poor to an oxygen-rich environment after birth might cause the heart to stop repairing itself.

In a series of experiments with newborn mice, Sadek and his colleagues found they could extend the one-week window during which heart muscle cells regenerate. They did this by temporarily starving heart cells of oxygen or dosing the heart with drugs that absorb the harmful oxygen byproducts, called reactive oxygen species or free radicals.

One of Sadek’s next steps is to see if it’s possible to temporarily turn on the heart’s ability to regenerate itself in adulthood. The ultimate goal would be to develop new treatments for heart failure, a weakening of the heart muscle that carries a prognosis grimmer than many cancers, says Sadek. Fifty percent of heart failure patients die within 5 years of diagnosis.

Heart attacks are a major cause of heart failure. “After a heart attack, part of the heart muscle dies and is replaced by [scar] tissue, not functional muscle,” says Sadek. “All current therapies are dedicated to saving the rest of the heart that wasn’t injured and not on growing back muscle.”

Researchers are not yet certain if humans, like mice, are born with a similar window during which their hearts can regenerate. But if they are, the finding would revolutionize the treatment of congenital heart defects. Surgeons can already perform heart procedures in the womb and on the tiniest newborns. “But if you know the heart cells can grow and divide even after birth, that would perhaps help them develop new surgical strategies,” says Sadek, or potentially medical treatments if the congenital defect is limited to the heart muscle itself.

His and his colleagues’ findings have spurred many other research groups to use his technique to study heart regeneration in mammals. Many have successfully replicated Sadek’s results, but a few have had difficulty. (For more, read this story in The Scientist).

Sadek’s next step is to replicate his heart research on larger mammals to see if they, too, are able to repair their hearts for a short time after birth. If that goes well, he will move toward designing trials to study the same regenerative window in human newborns with congenital heart defects that cause damage to the heart muscle.

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