microRNA-1 inhibits cardiomyocyte proliferation in mouse neonatal hearts by repressing CCND1 expression

Previous studies have shown that urodele amphibians and zebrafish have extraordinary abilities to regenerate their heart following injuries (1,2). In adult zebrafish, they can regenerate their heart after 20% of the ventricle was removed. This was achieved without fibrotic scar formation and mainly through cardiomyocyte proliferation. However, this remarkable ability is not seen in mammalian hearts. It has been reported that cardiomyocytes in 2 day-old mouse neonates could still divide extensively in all regions of the heart (3,4). Unfortunately, this proliferative ability is greatly reduced by the time that the neonatal heart reaches 13 days old. In the adult mammalian heart, the cardiomyocytes are “irreversibly” growth arrested so are unable to self-renewal following myocardial damage. Surprisingly, Porrello et al. (5) reported that 1-day-old mouse neonates could completely regenerate their myocardium after 15% of their left ventricle was removed. Detailed analyses of the results revealed that the regeneration was achieved through the proliferation of pre-existing cardiomyocytes, while the architecture of the heart and physiological functions were also restored. However, 7-day-old neonates lose this regenerative ability and fibrotic scars replace the missing myocardium. In this context, it is important to elucidate the underlying mechanisms that regulate neonatal cardiomyocyte proliferation, which could potentially be translated in regenerative medicine to treat degenerative heart diseases