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A calcineurin-dependent transcriptional pathway for cardiac hypertrophy.

Authors: Molkentin, JD  Lu, JR  Antos, CL  Markham, B  Richardson, J  Robbins, J  Grant, SR  Olson, EN 
Citation: Molkentin JD, etal., Cell. 1998 Apr 17;93(2):215-28.
Pubmed: (View Article at PubMed) PMID:9568714

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.


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CRRD Object Information
CRRD ID: 1579956
Created: 2006-06-05
Species: All species
Last Modified: 2006-06-05
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.