title: The transcriptional repressor Nab1 is a specific regulator of pathological cardiac hypertrophy.
abstract: 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.
authors: Rudolf-Virchow-Center/DFG-Research Center for Experimental Biomedicine, University of Wuerzburg, Versbacher Strasse 9, 97078 Wuerzburg, Germany.
authors: Monika
authors: M
authors: Buitrago
authors: Kristina
authors: K
authors: Lorenz
authors: Alexander H
authors: AH
authors: Maass
authors: Silke
authors: S
authors: Oberdorf-Maass
authors: Ursula
authors: U
authors: Keller
authors: Eva M
authors: EM
authors: Schmitteckert
authors: Yuri
authors: Y
authors: Ivashchenko
authors: Martin J
authors: MJ
authors: Lohse
authors: Stefan
authors: S
authors: Engelhardt
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000378:metabolism*; D051765:Early Growth Response Transcription Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051765:Early Growth Response Transcription Factors; C490624:Nab1 protein, mouse; D012097:Repressor Proteins