Regulation of growth in the adult cardiomyocytes.

Cardiomyocytes of adult myocardium increase their cellular mass in response to growth stimuli. They undergo hypertrophic growth but they do not proliferate in contrast to immature cardiomyocytes. Growth stimuli of the adult cardiomyocytes include classical growth hormones, various neuroendocrine factors, and the increase in mechanical load. The signal transduction of alpha1-adrenoceptor stimulation has been investigated in greatest detail and may therefore be taken as a reference for other humoral stimuli. It involves the activation of protein kinase C (PKC) and, downstream of PKC activation, of two separate signaling pathways, one including the mitogen-activated protein kinase and another including PI3-kinase and p70(s6k) as key steps. Activation of the first pathway leads to re-expression of fetal genes, activation of the second pathway to a general activation of protein synthesis, and cellular growth. In neonatal cardiomyocytes, mechanical stretch causes growth by an activation of an autocrine mechanism including angiotensin II and endothelin. This mechanism does not operate, however, in adult cardiomyocytes. A mechanism of mechanotransduction has not yet been identified on adult cardiomyocytes but integrins may play a part. In microgravity, the scenario of myocardial growth stimulation is altered. On the systemic level, there are changes in hemodynamic and neuroendocrine regulation that exert indirect effects on the myocardium. Microgravity may also exert a direct cellular effect by the absence of a constant gravitational load component.