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Hopkins scientists discover how an out-of-tune protein leads to muscle demise in heart failure
Date:9/12/2012

A new Johns Hopkins study has unraveled the changes in a key cardiac protein that can lead to heart muscle malfunction and precipitate heart failure.

Troponin I, found exclusively in heart muscle, is already used as the gold-standard marker in blood tests to diagnose heart attacks, but the new findings reveal why and how the same protein is also altered in heart failure. Scientists have known for a while that several heart proteins troponin I is one of them get "out of tune" in patients with heart failure, but up until now, the precise origin of the "bad notes" remained unclear.

The discovery, published online ahead of print on Sept. 12 in the journal Circulation, can pave the way to new and badly needed diagnostic tools and therapies for heart failure, a condition marked by heart muscle enlargement and inefficient pumping, and believed to affect more than 6 million adults in the United States, the researchers say.

Troponin I acts as an on-off switch in regulating heart relaxation and contraction and, in response to, adrenaline the "flight-fight" response. But when altered, troponin I can start acting as a dimmer switch instead, one that ever so subtly modulates cardiac muscle function and reduces the heart's ability to pump efficiently and fill with blood, the researchers found.

The Hopkins team used a novel method to pinpoint the exact sites, or epicenters, along the protein's molecule where disease-triggering changes occur. They found 14 such sites, six of them previously unknown. In revealing new details about the molecular sequence of events leading up to heart failure, the researchers said their work may spark the development of tests that better predict disease risk and monitor progression once the heart begins to fail.

"Our findings pinpoint the exact sites on troponin I's molecule where disease-causing activity occurs, and in doing so they give us new targets for treatment," says researcher J
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Contact: Ekaterina Pesheva
epeshev1@jhmi.edu
410-502-9433
Johns Hopkins Medicine
Source:Eurekalert

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