Taking pressure off the heart: the ins and outs of atrophic remodelling

Our work on atrophic remodelling of the heart has led us to appreciate the simple principles in biology: (i) the dynamic nature of intracellular protein turnover, (ii) the return to the foetal gene programme when the heart remodels, and (iii) the adaptive changes of cardiac metabolism. Although the molecular mechanisms of cardiac hypertrophy are many, much less is known regarding the molecular mechanisms of cardiac atrophy. We state the case that knowing more about mechanisms of atrophic remodelling may provide insights into cellular consequences of metabolic and haemodynamic unloading of the stressed heart. Overall we strive to find an answer to the question: 'What makes the failing heart shrink and become stronger?' We speculate that signals arising from intermediary metabolism of energy-providing substrates are likely candidates.