Activation of the calcineurin/NFAT signalling cascade starts early in human hypertrophic myocardium.

Cardiac hypertrophy is an independent risk factor for heart failure. Recent studies on gene regulation of proteins have involved intracellular Ca2+ homeostasis. The Ca2+-sensitive phosphatase, calcineurin, is one potential regulator of the hypertrophic response, so we aimed to investigate the calcineurin-dependent signal pathway at different stages of hypertrophy in human myocardium. We found the calcineurin pathway to be significantly activated in hypertrophic compared with non-hypertrophic myocardium as demonstrated by increased calcineurin activity and expression of calcineurin A-beta and B, and GATA-4, and a shift of phosphorylated cytoplasmic NFAT-3 into the nucleus as dephosphorylated nuclear NFAT-3. There was a tendency for these changes to be more pronounced in the decompensated compared with the compensated hypertrophic myocardium. The present study provides evidence for significant activation of the Ca2+-triggered calcineurin pathway in hypertrophic humans. Already present in compensated hypertrophy it showed a tendency to a further increase following transition to decompensated hypertrophy.