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Signaling Protein Helps Limit Damage In Heart Attack, Study Shows

Date:
March 24, 2008
Source:
Thomas Jefferson University
Summary:
Scientists have shown that a signaling protein helps protect the heart and adapt during a heart attack. The protein Gi has increased activity in failing hearts, but researchers have never been sure if it was helping the heart adapt to damage or if it was causing heart cells to die. The team blocked the protein in the hearts of genetically engineered mice experiencing heart attacks. The animals had greater heart damage than did normal mice.
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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.

Gi is important in intracellular signaling, akin to a molecular switch, Dr. Koch notes. It's 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 Gi's role and behavior. "We don't have to worry about what receptor we are blocking; we're 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. Koch's 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.

"It appears that in this setting, Gi is an important protective mechanism," Dr. Koch says. "The heart wants to activate Gi and attempt to protect cardiac myocytes from dying. We found that in this acute setting, heart attacks are bigger when Gi is blocked." As a result, the heart can't pump as well.

They would like to find out Gi's role in chronic heart failure, where there is much less cell death occurring, and Gi levels remain high. In the chronic phase, Dr. Koch points out, Gi activity could be "maladaptive." They plan to test the idea in chronic heart failure animal models.

*The team reports its findings March 18, 2008, in the journal Circulation. 


Story Source:

Materials provided by Thomas Jefferson University. Note: Content may be edited for style and length.


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Thomas Jefferson University. "Signaling Protein Helps Limit Damage In Heart Attack, Study Shows." ScienceDaily. ScienceDaily, 24 March 2008. <www.sciencedaily.com/releases/2008/03/080321174214.htm>.
Thomas Jefferson University. (2008, March 24). Signaling Protein Helps Limit Damage In Heart Attack, Study Shows. ScienceDaily. Retrieved March 29, 2024 from www.sciencedaily.com/releases/2008/03/080321174214.htm
Thomas Jefferson University. "Signaling Protein Helps Limit Damage In Heart Attack, Study Shows." ScienceDaily. www.sciencedaily.com/releases/2008/03/080321174214.htm (accessed March 29, 2024).

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