Changes in protein can precipitate heart failure………

Scientists have discovered that changes in a key cardiac protein can lead to heart muscle malfunction and precipitate heart failure.

Researchers from the Johns Hopkins University have found that Troponin I, a protein found in heart muscle is altered in heart failure.

Troponin I acts as an on-off switch in regulating heart relaxation and contraction and, in response to, adrenaline — the “flight-fight” response.

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When altered, troponin I can start acting as a dimmer switch instead, one that 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.

“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,” researcher Jennifer Van Eyk, said.

The team analysed tissue from the hearts of patients with end-stage heart failure and from deceased healthy heart donors.

The 14 sites the researchers identified are sites where troponin I binds with phosphate, a process known as phosphorylation.

Phosphate can activate or deactivate many enzymes, thus altering the function of a protein and, in the case of heart failure, ignite disease.

The six newly identified sites represent new ‘hot spots’ involved in heart contraction, the researchers said, and could be used as diagnostic markers or a target for treatment to restore function.

“Our goal would be to zero in on these new sites, gauge risk of heart failure and, hopefully, restore heart muscle function,” Van Eyk said in a statement.

The discovery was published in the journal Circulation


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