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New 'molecular switch' protein protects the heart from major cardiovascular damage

It's just one little amino acid, but it makes all the difference in protecting the heart from the harmful effects of heart attack and cardiac failure. Researchers from the University of Michigan Medical School suggest this amino acid, called histidine, could be the key to a new therapy for cardiovascular disease.

In a study to be published Jan. 22 in Nature Medicine as an advance online publication, U-M scientists describe how they created a modified form of a heart muscle protein called troponin I and how it improved cardiac function in mice and in damaged human heart cells. The secret was using genetic engineering technology to replace one amino acid called alanine, found in the adult form of troponin I, with a histidine from the fetal form of the same protein.

"The most important finding of our study was that this modified troponin I protein dramatically improved heart function under a variety of conditions associated with cardiovascular damage and heart failure," says Sharlene Day, M.D., an assistant professor of internal medicine in U-M's Cardiovascular Center and co-first author of the Nature Medicine paper.

"This study provides the first evidence that a single histidine substitution in troponin I can improve short and long-term cardiac function in laboratory mice with heart failure," says Joseph M. Metzger, Ph.D. a professor of molecular and integrative physiology and of internal medicine in the U-M Medical School. "The fact that we also were able to rescue the functionality of damaged human heart cells is a significant advance."

Metzger believes U-M's modified troponin I protein could become the basis of a new gene therapy or cell-based therapy for heart disease and heart failure. Progressive heart failure affects 4.8 million Americans. Despite current medical and surgical therapies, mortality remains high.

Troponin I is an important cardiac muscle regulatory protein that controls the calcium sensitivity of heart mu
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Contact: Sally Pobojewski
pobo@umich.edu
734-615-6912
University of Michigan Health System
22-Jan-2006


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