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Faulty cell membrane repair causes heart disease

During vigorous exercise, heart muscle cells take a beating. In fact, some of those cells rupture, and if not for a repair process capable of resealing cell membranes, those cells would die and cause heart damage (cardiomyopathy).

Researchers at the University of Iowa Roy J. and Lucille A. Carver College of Medicine have discovered a specific repair mechanism in heart muscle and identified a protein called dysferlin that is critical for resealing heart muscle cell membranes.

The study, led by UI researcher and Howard Hughes Medical Institute investigator Kevin Campbell, Ph.D., also shows that loss of dysferlin causes cardiomyopathy in mice. Furthermore, heart damage in these mice is exaggerated by vigorous exercise or by inherent muscle weakness caused by a muscular dystrophy defect. The results are published in the July 1 issue of the Journal of Clinical Investigation.

Active tissues, like a beating heart or contracting muscle, need mechanisms to repair the inevitable cell membrane tears caused by physical stress and strain. In 2003, Campbell and his colleagues identified dysferlin as a key protein in this vital repair mechanism in skeletal muscle. In humans, dysferlin deficiency -- which leads to faulty muscle membrane repair -- causes three types of muscular dystrophy.

The new study expands knowledge of dysferlin function, showing that dysferlin-mediated membrane repair is also important in heart muscle cells and suggests that inadequate membrane repair can also lead to cardiomyopathy.

"If we could boost this repair mechanism, it might be possible to slow cardiac and skeletal muscle damage in muscular dystrophy patients," said Campbell who also holds the Roy J. Carver Biomedical Research Chair in Molecular Physiology and is head of the department and a UI professor of neurology.

The UI team initially found that young mice that lacked dysferlin showed no heart damage, which is consistent with what is
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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-335-9917
University of Iowa
3-Jul-2007


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