The way through which an out-of-tune protein precipitates heart failure by causing its muscle to malfunction has been revealed by researchers.
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 the precise origin of the "bad notes" remained unclear.
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, the journal "Circulation" reports.
"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 Jennifer Van Eyk, director of the Johns Hopkins Proteomics Innovation Centre in Heart Failure.
Troponin I acts as an on-off switch in regulating heart relaxation and contraction. In response to adrenaline, this protein also triggers the "flight-fight" response, according to a Johns Hopkins statement.
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 epicentres, along the protein's molecule where disease-triggering changes occur. They found 14 such sites, six of them previously unknown. They said their work may spark the development of tests that better predict disease risk and monitor progression of the disease once the heart begins to fail.