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Mayo Clinic researchers discover gene mutations that 'ignore' stress, lead to heart failure

ROCHESTER, Minn. -- Mayo Clinic researchers have discovered genetic mutations in heart patients that make them vulnerable to heart failure because they produce an abnormal protein that can't decode stress messages from the body.

Mayo researchers are the first to realize that these proteins do not recognize the stress alarm. As a result, they can't properly respond to cue adjustments within the heart that normally manage stress. These defects make the heart muscle susceptible to damage. The Mayo Clinic research team's report appears in the journal Nature Genetics, v. 36; no. 4, April 2004 (www.nature.com).

Research team leader Andre Terzic, M.D., Ph.D., a specialist in cardiac biology, describes the work as groundbreaking because it reveals critical molecular mechanisms which may in turn point to possible new treatments for heart failure. "Very little is known about stress tolerance of the heart in health and disease," says Dr. Terzic. "This discovery opens a new field of investigation in cardiovascular medicine as we uncover how and why the heart becomes vulnerable to stress."

In addition to collaborating with other researchers from Mayo Clinic, Dr. Terzic's team drew upon the expertise of the University of Minnesota Supercomputing Center to help model the shape of the protein under investigation.

Significance of the Findings

The significance of the Mayo Clinic findings is threefold. It: 1) for the first time, views heart failure as a communication or signaling problem in the stress-management system of heart cells, 2) tests the idea in human beings, and 3) offers convincing evidence that miscommunication of stress signals distresses the heart and plays a role in susceptibility to heart failure.

This work differs from most research into genetic causes of heart failure which has identified defects in proteins involved in the mechanics of cardiac pumping, not in the communicat
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Contact: Bob Nellis
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
29-Mar-2004


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