For heart repair, call RNA

After attack, small molecules help contracting cells regenerate in mice

cardiac muscle cells

CHANGE OF HEART  Researchers used small RNA molecules to make mouse cardiac muscle cells (such as this one highlighted in green and blue) start dividing again after a heart attack. 

Lab of Ed Morrisey, Ph.D./Perelman School of Medicine/University of Pennsylvania

When people suffer a heart attack, they can’t regrow muscle cells that have died after being deprived of oxygen. But mice injected with small RNA molecules following heart attacks do regenerate cardiac muscle, researchers report in the March 18 Science Translational Medicine.

Scientists knew that a cluster of microRNAs, tiny molecules that keep genes from being turned on, are active in animal embryos at the same time that heart cells grow and divide. The RNA suppresses signals that tell organs to stop making new cells, a team of American and Chinese researchers found.

When the researchers deleted the microRNA group in mouse embryos, the rodents had less cell growth during the early stages of development. Making the microRNAs more active led to mice born with overlarge hearts.

The researchers then switched on production of the RNA molecules in adult mice that had suffered heart attacks. The rodents grew back heart muscle cells and had little scarring, which normally prevents the healing heart from contracting well.

After six to 12 weeks, though, the rodents’ hearts failed. “The muscle cells would continue to want to divide, and dividing cells don’t contract as well as nondividing cells,” says study coauthor Edward Morrisey, a developmental biologist at the University of Pennsylvania.

But when Morrisey and his team injected post–heart attack mice for seven days with short-lived molecules that simulate the effects of the microRNA, most of the animals survived.

“This is probably going to be a very useful way to promote cardiac regeneration, but the timing of it’s going to be really critical,” Morrisey says. “You’re going to want to do it for a very short window of time after cardiac injury.”

Next, Morrisey wants to see if the technique works in larger animals such as pigs.

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