[Molecular regulation of myocardial apoptosis]

Since apoptosis was described as a process distinct from necrosis, there have been many studies of programmed cell death in diseases, especially immunological diseases. Because cardiac myocytes are terminally differentiated cells, they have typically been assumed to die exclusively by necrosis. However, during the last six to seven years this view has been challenged by several studies demonstrating that a significant number of myocytes undergo apoptosis in myocardial infarction, heart failure, myocarditis, arrhythmogen right ventricular dysplasia, and immune rejection after cardiac transplantation, as well as in other conditions of stress. These are potentially very important observations, because apoptosis--unlike necrosis--can be blocked or reversed at early stages. The tracking of cytoprotective and apoptotic signal transduction pathways has proceeded rapidly with important new insights into the roles of mitochondria-dependent pathway, Bcl-2 protein family, p38 mitogen-activated protein kinase, extracellular signal-regulated kinase and c-Jun N-terminal kinase in cell fate. New studies have demonstrated that specific inhibition of apoptosis and activation of cytoprotective mechanisms, based on the better understanding of the intracellular signaling pathways, can significantly protect cardiac myocytes. This review will assess progress in cardiac myocyte apoptosis research and report on the current status of anti-apoptotic therapy in acute and chronic heart diseases.