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Doubling down on heart failure: Researchers discover new route to disease, and drugs to match
Date:6/7/2012

A new study in the journal Circulation packs a powerful one-two punch in the fight against heart failure. The leading blow: Identification of a unique alliance of proteins that plays a major role in the development of the disease. The second but equally powerful hit: Drugs that interfere with this axis already exist.

Though still in its infancy, the combination is just the type of research the scientific community is looking for in its efforts to speed up the development of the next generation of treatments for the nation's biggest killers, of which heart disease is the long-reigning champ.

Burns C. Blaxall, Ph.D., FAHA, of the University of Rochester Medical Center, led the research team to the discovery, which revolves around adrenaline, the hormone that regulates rate and strength of the heart and causes our hearts to beat furiously in a crisis. Adrenaline levels are constantly ramped in people with heart failure the body's attempt to recharge a weakened heart. While decades of research have established a connection between elevated adrenaline and heart failure, there is still much to learn about how it contributes to the disease.

In a mouse model of heart failure, Blaxall's team found that chronically high levels of adrenaline spur a bad actor a protein called PAR1 into gear. Several years ago, collaborative work in Blaxall's laboratory showed that over-stimulating PAR1 in cardiac muscle cells leads to heart failure, while blocking it protects against the disease.

But, like most processes in the body, adrenaline doesn't drive PAR1 on its own; the team discovered it tags a middleman another protein, called MMP-13 which then prompts activation of PAR1 to wreak havoc in the heart.

"This research is very exciting because we've identified a completely new pathway activated by adrenaline that contributes to heart failure," said Blaxall, an associate professor at the Aab Cardiovascular Research Institut
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Contact: Emily Boynton
emily_boynton@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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