%0 Journal Article %1 Lewin2009 %A Lewin, G. %A Matus, M. %A Basu, A. %A Frebel, K. %A Rohsbach, S. P. %A Safronenko, A. %A Seidl, M. D. %A Stumpel, F. %A Buchwalow, I. %A Konig, S. %A Engelhardt, S. %A Lohse, M. J. %A Schmitz, W. %A Muller, F. U. %D 2009 %J Circulation %K AMP AMP/metabolism Analysis Animals Array C57BL Cardiomegaly/*genetics/metabolism/*physiopathology Cyclic Electrophoresis, Element Element-Binding Expression Function, Gel, Gene Left/physiology Mass Messenger/metabolism Mice Modulator/*metabolism Oligonucleotide Profiling Protein/*metabolism Proteomics RNA, Response Sequence Spectrometry Transgenic Two-Dimensional Ventricular beta-1/genetics/*metabolism Receptor Adrenergic %N 1 %P 79-88 %T Critical role of transcription factor cyclic AMP response element modulator in beta1-adrenoceptor-mediated cardiac dysfunction %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19103994 %V 119 %X BACKGROUND: Chronic stimulation of the beta(1)-adrenoceptor (beta(1)AR) plays a crucial role in the pathogenesis of heart failure; however, underlying mechanisms remain to be elucidated. The regulation by transcription factors cAMP response element-binding protein (CREB) and cyclic AMP response element modulator (CREM) represents a fundamental mechanism of cyclic AMP-dependent gene control possibly implicated in beta(1)AR-mediated cardiac deterioration. METHODS AND RESULTS: We studied the role of CREM in beta(1)AR-mediated cardiac effects, comparing transgenic mice with heart-directed expression of beta(1)AR in the absence and presence of functional CREM. CREM inactivation protected from cardiomyocyte hypertrophy, fibrosis, and left ventricular dysfunction in beta(1)AR-overexpressing mice. Transcriptome and proteome analysis revealed a set of predicted CREB/CREM target genes including the cardiac ryanodine receptor, tropomyosin 1alpha, and cardiac alpha-actin as altered on the mRNA or protein level along with the improved phenotype in CREM-deficient beta(1)AR-transgenic hearts. CONCLUSIONS: The results imply the regulation of genes by CREM as an important mechanism of beta(1)AR-induced cardiac damage in mice.

@article{Lewin2009, abstract = {BACKGROUND: Chronic stimulation of the beta(1)-adrenoceptor (beta(1)AR) plays a crucial role in the pathogenesis of heart failure; however, underlying mechanisms remain to be elucidated. The regulation by transcription factors cAMP response element-binding protein (CREB) and cyclic AMP response element modulator (CREM) represents a fundamental mechanism of cyclic AMP-dependent gene control possibly implicated in beta(1)AR-mediated cardiac deterioration. METHODS AND RESULTS: We studied the role of CREM in beta(1)AR-mediated cardiac effects, comparing transgenic mice with heart-directed expression of beta(1)AR in the absence and presence of functional CREM. CREM inactivation protected from cardiomyocyte hypertrophy, fibrosis, and left ventricular dysfunction in beta(1)AR-overexpressing mice. Transcriptome and proteome analysis revealed a set of predicted CREB/CREM target genes including the cardiac ryanodine receptor, tropomyosin 1alpha, and cardiac alpha-actin as altered on the mRNA or protein level along with the improved phenotype in CREM-deficient beta(1)AR-transgenic hearts. CONCLUSIONS: The results imply the regulation of genes by CREM as an important mechanism of beta(1)AR-induced cardiac damage in mice.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Lewin, G. and Matus, M. and Basu, A. and Frebel, K. and Rohsbach, S. P. and Safronenko, A. and Seidl, M. D. and Stumpel, F. and Buchwalow, I. and Konig, S. and Engelhardt, S. and Lohse, M. J. and Schmitz, W. and Muller, F. U.}, biburl = {https://www.bibsonomy.org/bibtex/29536477044b9adcc5dd1efd7e929a202/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {de916dab681a0fdfcd844a9049cf4d13}, intrahash = {9536477044b9adcc5dd1efd7e929a202}, issn = {1524-4539 (Electronic) 1524-4539 (Linking)}, journal = {Circulation}, keywords = {AMP AMP/metabolism Analysis Animals Array C57BL Cardiomegaly/*genetics/metabolism/*physiopathology Cyclic Electrophoresis, Element Element-Binding Expression Function, Gel, Gene Left/physiology Mass Messenger/metabolism Mice Modulator/*metabolism Oligonucleotide Profiling Protein/*metabolism Proteomics RNA, Response Sequence Spectrometry Transgenic Two-Dimensional Ventricular beta-1/genetics/*metabolism Receptor Adrenergic}, month = {Jan 6}, note = {Lewin, Geertje Matus, Marek Basu, Abhijit Frebel, Karin Rohsbach, Sebastian Pius Safronenko, Andrej Seidl, Matthias Dodo Stumpel, Frank Buchwalow, Igor Konig, Simone Engelhardt, Stefan Lohse, Martin J Schmitz, Wilhelm Muller, Frank Ulrich Research Support, Non-U.S. Gov't United States Circulation Circulation. 2009 Jan 6;119(1):79-88. Epub 2008 Dec 22.}, number = 1, pages = {79-88}, shorttitle = {Critical role of transcription factor cyclic AMP response element modulator in beta1-adrenoceptor-mediated cardiac dysfunction}, timestamp = {2010-12-14T18:22:41.000+0100}, title = {Critical role of transcription factor cyclic AMP response element modulator in beta1-adrenoceptor-mediated cardiac dysfunction}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19103994}, volume = 119, year = 2009 }