A Novel Non-Apoptotic Role for Caspase Activity during Cardiac Hypertrophy

Abstract

Cardiac hypertrophy is an adaptive response in which the heart grows to normalize output during times of increased demand. This increase in size originates from the growth of cardiomyocytes rather than cellular division. Many cellular modifications observed during hypertrophy are reminiscent of apoptosis; caspase proteases, traditionally known for their role in apoptosis, have recently been implicated in non-apoptotic settings including cardiac differentiation. Studies have reported caspase-3 inhibition limits the heart`s ability to undergo pathological hypertrophy in vivo. Data presented here indicate that inhibition of caspase-3 and caspase-8 minimizes hypertrophic growth in primary cardiomyocytes. Phenylephrine induced an increase in cell size, which was attenuated upon addition of caspase inhibitors. These data suggest these proteins may be involved in hypertrophic growth of cardiomyocytes. Furthermore, results suggest that increased caspase activity may not be directly responsible for this effect. Rather, subcellular localization of caspase proteases may contribute to the effects seen during hypertrophy.