Walter Koch, Ph.D., director of the Center for Translational Medicine of the Department of Medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and his colleagues at Duke used a virus to carry a gene into the heart cells of individuals who had suffered heart failure. The gene blocks the activity of an enzyme that is increased in such heart cells, in turn, enabling the cells to beat at normal strength. Dr. Koch and his co-workers at Duke University Medical Center in Durham, N.C., presented their findings this week at the American Heart Association's Scientific Sessions 2003 in Orlando.
According to Dr. Koch, who is W.W. Smith Professor of Cardiology at Jefferson Medical College of Thomas Jefferson University, researchers have known for some time that the beta-adrenergic receptor system fails to work properly in individuals with end-stage heart failure. Such receptors "drive the heart both by rate and force of contraction," he says.
The researchers' target has been the beta-adrenergic kinase (ARK1), an enzyme that is elevated in human heart failure. One of its functions is to turn off beta-adrenergic receptors. "In heart failure, beta adrenergic receptor density is decreased, ARK is increased and both together cause dysfunctional beta receptor signaling," Dr. Koch says. "A failing heart then has little capacity to respond to exercise or stress because there are fewer receptors and the remaining receptors are more or less turned off.
"We have thought that inhibiting ARK could increase signaling and increase function," he explains.
In the laboratory dish, the researchers infected heart cells from patients who underwent cardiac transplantation due to end
Contact: Steve Benowitz
Thomas Jefferson University