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Clean-up duty

Joseph Metzger, Ph.D., and his lab team are giving dysfunctional hearts new instructions. (Photo: Brady Willette)

University team creates a novel ‘calcium sponge’ to help erase one of the country’s leading causes of heart failure

Imagine your heart muscle as a tiny symphony orchestra. Led by a conductor, that heart-muscle orchestra squeezes and relaxes, about one beat per second, in a never-ending tempo. For most of us, the conductor leads the orchestra so well that we never stop to appreciate the wonder of it as our hearts beat on, 100,000 times a day, 35 million times a year.

Joseph Metzger, Ph.D., head of the Department of Integrative Biology and Physiology in the University of Minnesota Medical School, uses the orchestra analogy to explain not just how the heart muscle works, but to help nonscientists make sense of his recent research.

“We’re focused on understanding how the heart muscle works,” says Metzger, referring to his laboratory staff of 18 investigators engaged in molecular cardiovascular research. “It’s a journey of understanding that begins at the level of the gene.”

As he explains, the “conductor” of the heartbeat is calcium, which ebbs and flows as the heart works. Calcium levels shoot up when the heart contracts, then drop sharply as it relaxes. Specialized proteins respond to the calcium levels, prompting the heart’s squeezing-contracting rhythm.

But as hearts age or are weakened by disease, calcium levels may not drop as they should when the heart muscle relaxes. Like the orchestra hanging onto a note too long, the calcium lingers, interfering with the signal to the protein that prompts the “relax” half of the heartbeat.

“Although the squeezing action is normal,” Metzger explains, “the relaxation becomes dysfunctional. This is called diastolic heart failure, and it’s a growing medical problem in the developed world.”

In fact, the problem is huge: Heart failure is the leading cause of hospitalizations in the United States—and the leading cause of death. Diastolic heart failure, for which doctors currently have no therapies, afflicts about half of all heart patients.

“For this type of heart failure, where calcium languishes in the heart cells, we’ve been working on how modify the signal, how to ‘sop up’ that extra calcium as the heart relaxes,” says Metzger.

That’s where Metzger’s so-called “calcium sponge” enters the picture. In February, the preeminent science journal Nature Medicine published Metzger’s paper that details his team’s discovery: a way to modify the blueprints for the body’s calcium buffers, giving the heart muscle new instructions.

“Our understanding of diastolic heart failure has been limited,” says Daniel Garry, M.D., Ph.D., chief of the Cardiovascular Division in the Department of Medicine. “Joe’s work has given us quite a lot of new information [and] has, in effect, established a launching pad for developing new medications that could impact calcium levels in the heart.”

Metzger’s team has introduced its calcium sponge into mice that model diastolic heart failure, and the sponge has successfully corrected their calcium malfunction.

“The leap from lab animals to humans is not trivial,” cautions Metzger, “but if it’s possible to modify the calcium level in a mouse, whose heart beats 700 times per minute, then it seems promising that we could do it in a human heart that beats 10 times more slowly.”

To find out how you can support this work, contact Amanda Storm Schuster at 612-626-2475 or aschuste@umn.edu.

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