Nature Medicine
11, 837 - 844 (2005)
Published online: 17 July 2005; | doi:10.1038/nm1272
The transcriptional repressor Nab1 is a specific regulator of pathological cardiac hypertrophyMonika Buitrago1, 2, Kristina Lorenz2, Alexander H Maass3, Silke Oberdorf-Maass1, Ursula Keller1, Eva M Schmitteckert2, Yuri Ivashchenko4, Martin J Lohse2
& Stefan Engelhardt11
Rudolf-Virchow-Center/DFG-Research Center for Experimental Biomedicine, University of Wuerzburg, Versbacher Strasse 9, 97078
Wuerzburg, Germany. 2
Institute of Pharmacology and Toxicology, University of Wuerzburg, Versbacher Strasse 9, 97078
Wuerzburg, Germany. 3
Medizinische Universitaetsklinik, University of Wuerzburg, Josef-Schneider-Strasse 2, 97080
Würzburg, Germany. 4
Sanofi-Aventis, Cardiovascular Division, Industriepark Höchst H823, 65926
Frankfurt am Main, Germany.
Correspondence should be addressed to Stefan Engelhardt stefan.engelhardt@virchow.uni-wuerzburg.de Hypertrophy represents the major physiological response of the heart to adapt to chronically enhanced workload, but is also crucial in the development of heart failure. Although we know of numerous inducers of cardiac hypertrophy, little is known about mechanisms that limit cardiac hypertrophy. Here, we describe the transcriptional repressor NAB1 as an endogenous regulator of cardiac growth. We identified NAB1 as being upregulated in both mouse and human heart failure. Nab1 is highly expressed in mammalian cardiac myocytes and it inhibited cardiomyocyte hypertrophy through repression of its targets, transcription factor Egr. Transgenic mice with cardiac-specific overexpression of Nab1 showed that Nab1 is a potent inhibitor of cardiac growth in response to pathological stimuli in vivo. Nab1 overexpression suppressed adrenergically induced and pressure overload−induced hypertrophy, whereas physiological growth during development and in response to exercise was not affected. These findings implicate the Nab1-Egr1 axis as a crucial regulator of pathological cardiac growth.
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