CHAPEL HILL, N.C. -- A new study has identified a molecular key to the development of heart failure, the most common form of cardiac disease.

Researchers led by Dr. Howard A. Rockman, associate professor of medicine and pharmacology at the University of North Carolina at Chapel Hill School of Medicine, prevented heart failure in a strain of mice genetically engineered to develop the disease. They were able to do so by blocking an enzyme known to be elevated in failing human hearts.

In a report in the June 9 issue of the Proceedings of the National Academy of Sciences, the authors characterize the findings as "dramatic" and say they may point the way toward new drugs to prevent and treat heart failure in people.

"Our goal is to understand the molecular mechanisms of heart failure--to understand what molecules or pathways are involved in the formation of heart failure and why the heart progressively fails until it can no longer function," Rockman says. xvThe UNC cardiologist and co-authors from Duke University and the University of California at San Diego focused on the beta-adrenergic receptor on the surface of cardiac tissue cells. These bind with the neurotransmitters epinephrine(adrenaline) and norepinephrine which increase the force and speed of the heart's beat, thus enabling the body to deal with stress, anxiety and exercise.

"It turns out that the beta-adrenergic receptor system is very abnormal in heart failure," Rockman explains, noting that studies conducted in the 1980s showed the system functions at "half the normal level in heart failure patients." Studies subsequently established that an enzyme called beta-adrenergic receptor kinase (BARK) is elevated in failing human heart tissue. This enzyme uncouples or "turns off" cardiac beta-adrenergic receptors, making less of them available for neurotransmitter binding.

In the new study, through genetic manipulation, Rockman and Drs. Walter Koch and Robert Lefkowitz a
'"/>

Contact: Robin Gaitens
rgaitens.est1@mail.unch.unc.edu
(919) 966-2860
University of North Carolina School of Medicine
9-Jun-1998