Mending a Broken Heart


mending a broken heartHeart disease is a leading cause of death and illness in the developed world and, once damaged, the heart has very limited capacity for regeneration. Following a heart attack, if blood flow is not restored to the heart muscle within 20-40 minutes, the muscle cells (cardiomyocytes) will die. The dead cells are replaced by scar tissue which does not contract or pump as well as healthy heart tissue.

Writing in the journal Nature, Jun Takeuchi and Benoit Bruneauat at the Gladstone Institute of Cardiovascular Disease have now identified a cocktail of three proteins that can turn mouse mesoderm into cardiac muscle cells (cardiomyocytes). Mesoderm is one of the three primary germ cell layers in the very early embryo – the others are the ectoderm and the endoderm – that can differentiate to give a number of tissues such as bone, blood, and muscle, including heart muscle. The three key proteins are the cardiac transcription factors, GATA4 and TBX5, which are believed to be involved in heart development and function, and a cardiac-specific subunit of BAF chromatin-remodelling complexes, Baf60c. Defects in the genes for these proteins have been linked to abnormal development and defects in the heart.

A combination of all three proteins was shown to direct differentiation of mouse mesoderm specifically into cardiac muscle cardiomyocytes that beat rhythmically, just like normal heart cells. Although, so far, only cells from very early mouse embryos have been turned into cardiomyocytes, Takeuchi and Bruneauat hope that their work will help to understand how new cardiomyocytes can be produced for use in regenerative medicine to treat heart disease.

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