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 calcin...

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Bibliographic Details
Published in:Journal of international medical research 2007-11, Vol.35 (6), p.803-818
Main Authors: Diedrichs, H, Hagemeister, J, Chi, M, Boelck, B, Mμller-Ehmsen, J, Schneider, CA
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Animals
Calcineurin - metabolism
Calcium - metabolism
Female
GATA4 Transcription Factor - metabolism
Heart Failure - etiology
Humans
Hypertrophy - metabolism
Hypertrophy - pathology
Male
Middle Aged
Myocardium - metabolism
Myocardium - pathology
NFATC Transcription Factors - metabolism
Protein Isoforms - metabolism
Risk Factors
Signal Transduction - physiology
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Summary: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-β 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.
ISSN:0300-0605
1473-2300
DOI:10.1177/147323000703500609