Signaling protein helps limit damage in heart attack, Jefferson scien...( (PHILADELPHIA) Scientists at the Cen...),Health

(PHILADELPHIA) Scientists at the Center for Translational Medicine at Thomas Jefferson University in Philadelphia have shown that a specific signaling protein is crucial to protecting the heart and helping it to adapt during a heart attack.

The protein Gi is known to have increased activity in the failing heart, but researchers have never been sure if it was helping the heart adapt to damage or if it was actually causing more heart cells to die. The Jefferson team, led by Walter Koch, Ph.D., W.W. Smith Professor of Medicine and director of the Center for Translational Medicine in the Department of Medicine at Jefferson Medical College, experimentally blocked the protein in the hearts of genetically engineered mice experiencing heart attacks. They found that the animals had greater heart damage than did similar mice with a working protein. The team reports its findings March 18, 2008, in the journal Circulation.

Gi is important in intracellular signaling, akin to a molecular switch, Dr. Koch notes. Its not a new drug target, he explains, but the activation of some receptors (such as beta-2 adrenergic receptors) that also turn on Gi could be targets.

Developing a class-specific Gi inhibitor, Dr. Koch explains, is an important step to understanding Gis role and behavior. We dont have to worry about what receptor we are blocking; were blocking a receptor that couples with Gi. We never had the tools before to tell if Gi activation was good or bad. We think that we can now begin to test the role of Gi in cardiac injury.

In the work, Dr. Kochs group developed a transgenic mouse with a functional knockout of the Gi gene, meaning that it lacked a working gene. The scientists then simulated a heart attack, catheterization and reperfusion by tieing off a coronary artery for 30 minutes and subsequently reestablishing the blood flow, causing an inflammatory response and tissue damage.

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