title: Critical role of transcription factor cyclic AMP response element modulator in beta1-adrenoceptor-mediated cardiac dysfunction.
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.
  
  
  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.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Münster, Münster, Germany.
authors.forename: Geertje
authors.initials: G
authors.lastname: Lewin
authors.forename: Marek
authors.initials: M
authors.lastname: Matus
authors.forename: Abhijit
authors.initials: A
authors.lastname: Basu
authors.forename: Karin
authors.initials: K
authors.lastname: Frebel
authors.forename: Sebastian Pius
authors.initials: SP
authors.lastname: Rohsbach
authors.forename: Andrej
authors.initials: A
authors.lastname: Safronenko
authors.forename: Matthias Dodo
authors.initials: MD
authors.lastname: Seidl
authors.forename: Frank
authors.initials: F
authors.lastname: Stümpel
authors.forename: Igor
authors.initials: I
authors.lastname: Buchwalow
authors.forename: Simone
authors.initials: S
authors.lastname: König
authors.forename: Stefan
authors.initials: S
authors.lastname: Engelhardt
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lohse
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schmitz
authors.forename: Frank Ulrich
authors.initials: FU
authors.lastname: Müller
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D000242:Cyclic AMP / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: C497411:Crem protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP