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Molecule involved in heart failure now implicated in heart attack damage
Date:9/15/2010

(PHILADELPHIA) A molecule known to be involved in progressive heart failure has now been shown to also lead to permanent damage after a heart attack, according to researchers at Thomas Jefferson University.

To prove this novel conclusion, the research team used gene therapy to inhibit the small protein, kinase known as G protein-coupled receptor kinase 2 (GRK2), and found heart muscles cells in mice were substantially protected against destruction that would otherwise occur after an induced myocardial infarction (MI), or heart attack.

Conversely, mice engineered to express excess GRK2 had more damage than would have been expected after an MI, the researchers say in the article currently found online at Circulation Research and to be published in the October 29th issue.

These finding suggest that humans experiencing a heart attack might be helped with delivery of a therapeutic targeting inhibition of GRK2, says Walter J. Koch, Ph.D., Director of the Center for Translation Medicine at Jefferson.

"Our results clearly show that GRK2 promotes cell death after a heart attack, so an inhibitor of this molecule is likely beneficial in preventing permanent damage, if delivered quickly enough," he says. "Currently, we have a gene therapy approach but for this indication a small molecule would be preferred."

Dr. Koch says that while it may be years before this concept can be tested in patients experiencing an MI, he expects anti-GRK2 gene therapy will be tested in patients with heart failure much sooner. A Phase I clinical trial for GRK2-targeted gene therapy is preparing to be launched, pending federal approval.

Dr. Koch and his colleagues have been working for 15 years to link GRK2 to heart failure in patients. They have demonstrated that the protein puts a brake on the beta-adrenergic receptors that respond to hormones (adrenalin and noradrenalin) that drive the heart beat the rate and force of contracti
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Contact: Rick Cushman
richard.cushman@jefferson.edu
215-955-2240
Thomas Jefferson University
Source:Eurekalert

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