An alternative view of apoptosis in heart development and disease.

Although the involvement of caspases in cardiomyocyte death is widely accepted [reviewed in], increasing experimental evidence suggests that caspase activation is not relevant for post-mitotic cardiomyocyte cell death. Controversy also exists as to the mechanisms conferring cardioprotection by caspase inhibitors, which could be unrelated to apoptosis or target non-myocardial cells. In addition, the genes controlling the caspase-dependent death pathway are silenced during early post-natal development. Finally, the major role of death receptors and the Bcl-2-related proteins in the myocardium is probably to control differentiation, adaptation to stress and mitochondrial integrity. In light of these findings, we propose here an alternative explanation of the role of canonical apoptosis regulators in the control of cardiomyocyte life and death.