Abstract
Cardiomyocytes exhibit two distinctive modes of growth during development. Prenatal and early postnatal myocytes grow by the process of cell proliferation / hyperplasia and around the third day post birth; the cells exit the cell cycle irreversibly and grow via an increase in cell size/ hypertrophy (Ahuja et al., 2007). This critical transition establishes the number of cardiomyocytes and affects the ability of the heart to recover from injury. Yet, despite the importance of this developmental process the transition from hyperplasia to hypertrophy is not very well understood. One potential candidate for the regulation of this transition is the \r sympathetic nervous system. It is known that sympathetic innervation plays a vital role in the development of the heart and other systems; however the precise mechanism of the role is not well defined. To understand the mechanisms involved in the development of these myocytes, the role of sympathetic innervation in the development of postnatal cardiomyocytes was investigated.\r I investigated the role of the sympathetic system in cardiomyocyte proliferation using both in vivo and in vitro systems. In the in vitro paradigm, myocytes were cultured with and \r without sympathetic neurons to study the effect of the neurons on the myocyte development. The sympathetic system exerts its effect via the release of noradrenaline (Dowell, 1985). I investigated whether the effects of sympathetic neurons were mediated by β-adrenergic signaling by using an agonist, isoproterenol and antagonist, propranolol to stimulate and block the noradrenergic neurotransmission. These experiments revealed that the sympathetic innervation promotes cell proliferation and delays myocyte hypertrophy via β-adrenergic signaling. It was found that the sympathetic innervation is necessary and sufficient to delay cell hypertrophy. \r Hypertrophy is also characterized by change in levels of proteins in the cell. Proteins were extracted from control and experimental rats (sympathetic activity ablated) at different time points (in vivo). Quantification of vital protein expression levels, mainly cfos, was performed with the help of Western blot analysis. Preliminary results showed that there was an increase in the cfos protein level when 7 day lesion hearts were compared to the control. Additional experiments would need to be performed to establish these results. \r However the ability of sympathetic innervation to alter cardiomyocyte growth indicated that the sympathetic nervous system has a direct causal role in the regulation of heart growth. The study of such mechanisms increases our knowledge about the underlining developmental processes which affect the ability of the heart in the adult stage. This may lead to potential\r therapeutic targets and provide an insight on the mechanism responsible for programing of adult cardiovascular diseases.