RASSF1A inhibits cardiac hypertrophy in mouse and man

Myocardial hypertrophy — enlargement of cardiac muscle cells and cardiac muscle — plays a key role in heart failure. Defective Ras signalling has been linked with Noonan syndrome, Costello syndrome and other clinical syndromes involving cardiac hypertrophy. However, little is known of the molecules that limit cardiac growth.

An international research team from Egypt, the United States and the United Kingdom studied one such candidate, a protein called tumour suppressor Ras-association domain family 1 isoform A (RASSF1A), which interacts with Ras. They found that the expression of the protein was reduced by ~50% in both failing human hearts and hypertrophic mouse hearts.

Mice lacking RASSF1A that were subjected to a surgical model of cardiac hypertrophy had larger heart cells and heavier heart/body weight ratios than wild-type operated controls. Over-expressing RASSF1A in neonatal rat cardiomyocytes blocked the hypertrophic response in a tissue-culture model of cardiac hypertrophy.

Together, these results suggest that RASSF1A inhibits cardiac hypertrophy in mice, and possibly humans, probably by blocking the hypertrophy-promoting Raf1–extracellular regulated kinase (ERK)1/2 signalling pathway. Therapies designed to target this molecule might prove useful in treating heart failure.

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