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

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.

 

This story appears in Penn Medicine's Basic Science News Bites (December 2009). Also in this edition:

  • Orthopaedics Research
  • picThrowing Their Backs into Regenerative Medicine
  • In order for tissue grown in the lab to replace damaged or diseased tissue in the body, it needs to withstand complex mechanical loads – large forces regularly experienced over a lifetime of daily activities.
  • Cell Biology
  • picCheating a Cell's Demise
  • The lifespan of normal human cells is determined in part by telomeres – the DNA-protein structures that cap the beginnings and ends of chromosomes.
  • Neuroscience Research
  • picPrion-Busting Cocktails
  • Prions are proteins that act like germs, infecting healthy tissue and causing havoc in the body. Their extreme stability and shape-shifting abilities make prions exceptionally difficult drug targets.
  • Diabetes Research
  • picNew Insights on Insulin Resistance
  • The overwhelming majority of type 2 diabetics are insulin resistant, which means their bodies are unable to respond to and use the insulin they produce.
  • Genetics Research
  • picZebrafish Model of Common Genetic Disorder
  • Because zebrafish develop rapidly, are transparent when young, and can be easily bred in large numbers, this new animal model will dramatically increase the screening capacity for a common human inherited disorder.

 

 

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