Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy

Cardiac hypertrophy is a pathologic enlargement of the heart, an alteration that leads to contractile dysfunction and eventual organ failure. The hypertrophy phenotype originates from concentric growth of heart muscle cells and shares many biochemical features with programmed cell death, implying a common molecular origin. Here, we show cell-autonomous activation of a mitochondrial cell death pathway during initial stages of muscle cell hypertrophy, a signal that is essential and sufficient to promote hypertrophy. Targeting individual cell death proteins may offer an effective means to limit the initial stage of cardiac disease, and forgo the transition to heart failure.