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Cell. 1998 Apr 17;93(2):215-28.

A calcineurin-dependent transcriptional pathway for cardiac hypertrophy.

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  • 1Department of Molecular Biology and Oncology, The University of Texas Southwestern Medical Center at Dallas, 75225-9148, USA.

Abstract

In response to numerous pathologic stimuli, the myocardium undergoes a hypertrophic response characterized by increased myocardial cell size and activation of fetal cardiac genes. We show that cardiac hypertrophy is induced by the calcium-dependent phosphatase calcineurin, which dephosphorylates the transcription factor NF-AT3, enabling it to translocate to the nucleus. NF-AT3 interacts with the cardiac zinc finger transcription factor GATA4, resulting in synergistic activation of cardiac transcription. Transgenic mice that express activated forms of calcineurin or NF-AT3 in the heart develop cardiac hypertrophy and heart failure that mimic human heart disease. Pharmacologic inhibition of calcineurin activity blocks hypertrophy in vivo and in vitro. These results define a novel hypertrophic signaling pathway and suggest pharmacologic approaches to prevent cardiac hypertrophy and heart failure.

PMID:
9568714
[PubMed - indexed for MEDLINE]
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