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Clues to heart disease in unexpected places, Temple researchers discover
Date:4/12/2013

(Philadelphia, PA) A major factor in the advance of heart disease is the death of heart tissue, a process that a team of scientists at Temple University School of Medicine's (TUSM) Center for Translational Medicine think could be prevented with new medicines. Now, the researchers are one step closer to achieving that goal, thanks to their discovery of a key molecule in an unexpected place in heart cells mitochondria, tiny energy factories that house the controls capable of setting off cells' self-destruct sequence.

The study is the first to identify the molecule, an enzyme known as GRK2 (G protein-coupled receptor kinase 2), in mitochondria. It was led by Walter J. Koch, Ph.D., Professor and Chairman of the Department of Pharmacology at TUSM, and Director of the Center for Translational Medicine at TUSM.

"We have known that GRK2 is involved in the pathological development of certain heart diseases, such as chronic heart failure, and that its increased activity can lead to the death of heart cells. But its mechanism for the latter was unclear," Koch said. In addition, while the enzyme was known to be present in elevated levels in the hearts of patients with heart failure, the reasons for its rise were not fully understood.

Normally, GRK2 hangs out near the plasma membrane of heart cells, where it turns off certain signals transferred from the blood to the tissue. But the researchers at Temple found that it moves to mitochondria in response to two classic features of heart disease, ischemic insult and ensuing oxidative stress. These two processes, in which a momentary lapse in the delivery of oxygen-rich blood to diseased tissues causes a sudden increase in damaging reactive molecules, converge to stimulate the self-destruct program of heart cells. They ultimately cause whole sections of heart tissue to die, leaving behind scars that can severely compromise the ability of the heart to function properly.

Koch's team found that
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Contact: Jeremy Walter
Jeremy.Walter@tuhs.temple.edu
215-707-7882
Temple University Health System
Source:Eurekalert

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