Death Receptor Signaling in the Heart

esearch over the past 3 decades has established that loss of cardiomyocytes through regulated cell suicide mechanisms contributes critically to the pathogenesis of myocardial infarction, heart failure, and other cardiac syndromes. wo of the most important cell death programs in the context of heart disease are apoptosis and necrosis. These forms of cell death differ primarily with respect to the magnitude of collateral damage inflicted on surrounding tissue. In apoptosis, the plasma membrane remains intact until the dying cell undergoes phagocytosis, whereas in necrosis not only does the membrane become leaky, but the cell actively secretes proinflammatory molecules. Apoptosis has always been recognized as a gene-directed and regulated process. In contrast, necrosis was thought to be an uncontrolled form of cell death resulting from overwhelming physical and chemical trauma to a cell. A big surprise over the past 15 years, however, has been the realization that a significant proportion of necrotic cell deaths occurs through highly regulated mechanisms.