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 prolif erate in contrast to immature cardiomyocytes. Growth stimuli of the adult c ardiomyocytes include classical growth hormones, various neuroendocrine fac tors, and the increase in mechanical load. The signal transduction of alpha (1)-adrenoceptor stimulation has been investigated in greatest detail and m ay 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 p rotein kinase and another including PI3-kinase and p70(s6k), key steps. Act ivation of the first pathway leads to re-expression of fetal genes, activat ion of the second pathway to a general activation of protein synthesis, and cellular growth. In neonatal cardiomyocytes, mechanical stretch causes gro wth By an activation of an autocrine mechanism including angiotensin II and endothelin. This mechanism does not operate, however, in adult cardiomyocy tes. A mechanism of mechanotransduction has not yet been identified on adul t cardiomyocytes but integrins may play a part. In microgravity, the scenar io of myocardial growth stimulation is altered, On the systemic level, ther e are changes in hemodynamic and neuroendocrine regulation that erect indir ect effects on the myocardium, Microgravity may also exert a direct cellula r effect by the absence of a constant gravitational load component.