Calpain Inhibition in a Transgenic Model of Calpastatin Overexpression Facilitates Reversal of Myocardial Hypertrophy

Our data demonstrate that calpain-mediated cleavage results in nuclear accumulation of a truncated, constitutively active and degradation-resistant calcineurin isoform that sustains a long-term myocardial hypertrophic response to angiotensin-II beyond withdrawal of the stimulus. Cardiomyocyte specific calpain inhibition by transgenic calpastatin overexpression prevented the post-stimulus myocardial hypertrophic response.