Cardiomyopathy, a weakening of the heart muscle often associated with inadequate heart pumping, affects tens of thousands of people in the United States. Researchers have discovered a new molecular pathway controlled by a master-switch protein in the heart muscles called myocardin that may be key to understanding some forms of heart disease. This pathway links heart muscle structure to heart-cell survival.
Myocardin-mutant heart tissue. Credit: Michael Parmacek, MD.
The discovery, published in the Proceedings of the National Academy of Sciences, provides new insights into the molecular program that controls how heart cells differentiate in a developing embryo and mature, and more importantly, identifies myocardin-activated genes as candidates that may underlie some forms of heart failure and cardiomyopathy. Mice genetically altered to block expression of myocardin in the heart develop cardiomyopathy. Mutant mice had severe alterations in the cell structures that cause contractions as well as a tissue that promotes communication between cells.
What’s more, this finding provides insights into heritable forms of cardiomyopathy and heart failure, many of which are caused by mutations in genes controlled by myocardin. “Demonstrating that removing the mouse myocardin gene leads to heart failure suggests that drugs which block programmed cell death should be evaluated for treatment of some forms of heart failure,” notes senior author Michael Parmacek, MD, director of the Penn Cardiovascular Institute.
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