title: Inducible re-expression of HEXIM1 causes physiological cardiac hypertrophy in the adult mouse.
abstract: OBJECTIVE
  The transcription factor hexamethylene-bis-acetamide-inducible protein 1 (HEXIM1) regulates myocardial vascularization and growth during cardiogenesis. Our aim was to determine whether HEXIM1 also has a beneficial role in modulating vascularization, myocardial growth, and function within the adult heart.
  
  
  RESULTS
  To achieve our objective, we created and investigated a mouse line wherein HEXIM1 was re-expressed in adult cardiomyocytes to levels found in the foetal heart. Our findings support a beneficial role for HEXIM1 through increased vascularization, myocardial growth, and increased ejection fraction within the adult heart. HEXIM1 re-expression induces angiogenesis, that is, essential for physiological hypertrophy and maintenance of cardiac function. The ability of HEXIM1 to co-ordinate processes associated with physiological hypertrophy may be attributed to HEXIM1 regulation of other transcription factors (HIF-1-α, c-Myc, GATA4, and PPAR-α) that, in turn, control many genes involved in myocardial vascularization, growth, and metabolism. Moreover, the mechanism for HEXIM1-induced physiological hypertrophy appears to be distinct from that involving the PI3K/AKT pathway.
  
  
  CONCLUSIONS
  HEXIM1 re-expression results in the induction of angiogenesis that allows for the co-ordination of tissue growth and angiogenesis during physiological hypertrophy.
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, H.G. Wood Bldg. W307, 2109 Adelbert Road, Cleveland, OH 44106, USA. mxm126@case.edu
authors.forename: Monica M
authors.initials: MM
authors.lastname: Montano
authors.forename: Candida L
authors.initials: CL
authors.lastname: Desjardins
authors.forename: Yong Qui
authors.initials: YQ
authors.lastname: Doughman
authors.forename: Yee-Hsee
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Yanduan
authors.initials: Y
authors.lastname: Hu
authors.forename: Heather M
authors.initials: HM
authors.lastname: Bensinger
authors.forename: Connie
authors.initials: C
authors.lastname: Wang
authors.forename: Julian E
authors.initials: JE
authors.lastname: Stelzer
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Dick
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hoit
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Chandler
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Michiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D004452:Echocardiography; D050991:GATA4 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D005838:Genotype; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D047493:PPAR alpha / Q000378:metabolism; D010641:Phenotype; D010807:Physical Endurance; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016601:RNA-Binding Proteins; D013318:Stroke Volume; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; C118642:Hexim1 protein, mouse; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C489428:Myc protein, mouse; D047493:PPAR alpha; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D014157:Transcription Factors
keywords: Angiogenesis; HEXIM1; Hypertrophy