Direct biomechanical induction of endogenous calcineurin inhibitor Down Syndrome Critical Region-1 in cardiac myocytes.

Signaling through the protein phosphatase calcineurin may play a critical role in cardiac hypertrophy. The gene for Down Syndrome Critical Region-1 (DSCR1) encodes a protein that is an endogenous calcineurin inhibitor. This study was designed to test the hypothesis that DSCR1 is directly induced by biomechanical stimuli.

Identification of IEX-1 as a biomechanically controlled nuclear factor-kappaB target gene that inhibits cardiomyocyte hypertrophy.

Biomechanical strain is a stimulus for cardiomyocyte hypertrophy and heart failure, but the underlying molecular mechanisms remain incompletely understood. Using an in vivo murine model of pressure overload and an in vitro model of mechanical stimulation of primary cardiomyocytes, we identified iex-1 as a gene activated during the early response of cardiomyocytes to hypertrophic stimuli and as a gene product that inhibits hypertrophy without affecting cardiomyocyte viability. On stimulation of cardiomyocytes, iex-1 mRNA and protein expression increased and translocation of the gene product to the cardiomyocyte nucleus occurred.