Characterisation of postnatal growth of the murine heart

Abstract 

Using a new technique to isolate rod-shaped cardiomyocytes from small tissue pieces we were able to analyse the developmental profile of postnatal cardiomyocyte growth in the mouse. During the first 4 postnatal days the volume of the cardiomyocytes remains relatively constant despite a concomitant increase in heart weight, indicating growth due to cell division of the cardiomyocytes, also called hyperplasia. After postnatal day 5 the volume of the cardiomyocytes increases dramatically until postnatal day 14, when the increment of the volume curve decreases again. The cardiomyocytes reach their adult volume at around 3 months of age. These measurements present the first detailed analysis of the phase of so-called developmental hypertrophy, i.e. normal cardiomyocyte growth in the mouse, and provide an essential base-line for the analysis of growth parameters in mouse models for cardiomyopathies. We used this method to characterise the growth characteristics of cardiomyocytes from MLP (muscle LIM protein) knockout mice, a mouse model for dilated cardiomyopathy. During the first 2 postnatal weeks there is no significant difference in the growth parameters between MLP knockout and wildtype mice. However, in the adult animals cardiomyocytes from MLP knockout mice are not only characterised by a more irregular shape, but also by a high variability in size compared to cardiomyocytes from wildtype animals. This suggests that the alterations in ventricular morphology in the MLP heart are not due to a general elongation of the cardiomyocytes but to myocyte disarray and ventricular wall thinning caused by the heterogeneous volume of the cardiomyocyte population.