Ilk gene underlies heart failure
By Cold Spring Harbor Laboratory
Aug 19, 2006, 21:35
Two independent papers in the September 1 issue of G&D reveal a critical role for the ILK protein in regulating cardiac contractility – identifying a new genetic component of heart disease.
Congestive heart failure affects 2-3 million people in the United States annually. A large portion of congestive heart failure cases is caused by a condition known as cardiomyopathy. Cardiomyopathy is a mostly genetic disease of the heart muscle that causes the heart to become enlarged, and to pump less efficiently.
Independent research groups from the labs of Drs. William J. Muller (McGill University) and Wolfgang Rottbauer (University of Heidelberg) demonstrate that the ILK protein is integral to the heart's ability to adapt its force of contraction to meet the body's changing needs for oxygenated blood.
Dr. Rottbauer explains that, "The work reported here suggests for the first time that ILK and some of its binding partners are essential components of the cardiac mechanical stretch sensor, dysfunction of which is suspected to be responsible for a significant proportion of human heart failure."
ILK, or integrin-linked protein kinase, is a component of the integrin signaling pathway, which recognizes changes in the extracellular environment and sends signals within the cell to affect an appropriate cellular response. In particular, integrins direct the assembly of actin-based adhesion structures to propagate cellular forces, and are thus essential for cell migration, growth, and survival.
Using two different animal model systems, Drs. Muller and Rottbauer show that loss of ILK in heart cells results in cardiomyopathy and heart failure. Lead author Donald White, a post-doctoral fellow in Dr. Muller's lab emphasizes that, "The fact that ILK plays such a critical role in cardiac physiology in such different organisms is undoubtedly exciting. It reinforces the central importance of this molecule in such a vital physiological process."
Dr. Muller adds: "Our collaborators at the Montreal Heart Institute, Montreal's Shriners' Hospital and the BC Cancer Agency have really played a critical role in helping us understand the role of ILK in cardiac physiology. We hope that our work will provide an ideal model for testing therapeutic strategies for heart disease, including exciting new approaches involving the use of stem cells to repair damaged heart tissue."
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