A gradual decline in the numbers of cardiomyocyte during later life has been suggested as an important cause of heart failure in the elderly. During embryonic development, proliferation rates are high in the developing heart. However, in both humans and mice the high fetal cardiomyocyte proliferation rates are rapidly attenuated after birth and a low level of cardiomyocyte production continues thereafter.
Zebrafish have become an important laboratory model for heart regeneration as they are one of the few species in which the adult heart is capable of regeneration after injury. We have also determined that the adult zebrafish heart has a relatively high basal level of cardiomyocyte production, which can be readily measured by thymidine analogue pulse labelling of cardiomyocytes.
In this study we show how the basal rate of cardiomyocyte renewal changes throughout adult zebrafish life. We also demonstrate the extent to which this can be up regulated by swimming against imposed water flow, which is normally considered a model for physiological cardiac hypertrophy — and is cardiac specific. Finally, as P38MAP kinase inhibition has been shown to promote cardiac proliferation, we examine the effect of this drug on zebrafish of different ages and in combination with exercise.
We hope to develop a model system in which aerobic exercise, a normal physiological stimulus, can be used alongside pharmacological intervention to promote cardiac regeneration in a controlled and specific way. This will then be used to screen for pharmacological agents that are cardiac specific and can be used to rejuvenate the aging heart or regenerate the damaged one.