WEB EXCLUSIVE

Young at Heart

Protein returns youth to cardiac muscle.

Tuesday, February 28, 2006

Researchers at the University of Michigan say they can help people with heart disease by literally making them young at heart. They're doing this by coaxing a certain protein in adult hearts to behave the way it does in a growing fetus.

Babies' hearts keep beating even through the stress of birth because they make a different version of a protein called troponin I than adult hearts. Soon after birth, we stop making the fetal form of the protein and settle into permanently making the adult version. University of Michigan researchers Sharlene Day and Joseph Metzger, say the adult form of troponin I normally regulates how our hearts beat. It also allows our hearts to respond properly during the "fight or flight response" which we undergo when we sense imminent danger. But this adult version stops working properly in stressful situations like heart attacks.

"In the face of this challenge of a heart attack, this troponin I molecule turns down its activity and in effect [shuts] off the pumping function of the heart," says Metzger.

As reported in Nature Medicine, Day and Metzger's team found a way to improve adult troponin I by using DNA technology to make a combined fetal and adult version.

Day explains, "What we did was to take a very small piece of the DNA from the fetal form and insert it into the adult form." Indeed, it was a very small piece of DNA—they switched a single amino acid of the troponin I protein from an alanine to a histidine.

Even though this is a very small change, the team saw dramatic results. When they put this combined protein in to mice, they discovered that the animals with the new form of troponin I withstood heart attacks better than those with the normal adult version.

"Their hearts contracted more vigorously, their hearts did not enlarge as much as the hearts of the animals that did not make the protein," says Day.

The team found a similar improvement in contraction when, in the lab, they put the new protein into human heart cells taken from patients with heart disease.

Even when there's nothing wrong in the heart, this combined version of the protein functions normally, and maintains the fight or flight response that adult hearts normally have. The only situation in which it behaves differently is during heart failure.

As Metzger says, "It serves as a sensor function, much like a smoke detector does in your home."

Day and Metzger say it will be several years before this gene therapy is available to treat people—there are a few hurdles to overcome. One of the main ones is to find a safe way to get this new protein into the hearts of patients. Until then, we'll just have to keep our hearts young and healthy in the usual ways—exercising, eating right, and trying to keep our dose of daily stress low.

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