title: Akt1 is required for physiological cardiac growth.
abstract: BACKGROUND
  Postnatal growth of the heart chiefly involves nonproliferative cardiomyocyte enlargement. Cardiac hypertrophy exists in a "physiological" form that is an adaptive response to long-term exercise training and as a "pathological" form that often is a maladaptive response to provocative stimuli such as hypertension and aortic valvular stenosis. A signaling cascade that includes the protein kinase Akt regulates the growth and survival of many cell types, but the precise role of Akt1 in either form of cardiac hypertrophy is unknown.
  
  
  RESULTS
  To evaluate the role of Akt1 in physiological cardiac growth, akt1(-/-) adult murine cardiac myocytes (AMCMs) were treated with IGF-1, and akt1(-/-) mice were subjected to exercise training. akt1(-/-) AMCMs were resistant to insulin-like growth factor-1-stimulated protein synthesis. The akt1(-/-) mice were found to be resistant to swimming training-induced cardiac hypertrophy. To evaluate the role of Akt in pathological cardiac growth, akt1(-/-) AMCMs were treated with endothelin-1, and akt1(-/-) mice were subjected to pressure overload by transverse aortic constriction. Surprisingly, akt1(-/-) AMCMs were sensitized to endothelin-1-induced protein synthesis, and akt1(-/-) mice developed an exacerbated form of cardiac hypertrophy in response to transverse aortic constriction.
  
  
  CONCLUSIONS
  These results establish Akt1 as a pivotal regulatory switch that promotes physiological cardiac hypertrophy while antagonizing pathological hypertrophy.
authors.affiliation: Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: DeBosch
authors.forename: Iya
authors.initials: I
authors.lastname: Treskov
authors.forename: Traian S
authors.initials: TS
authors.lastname: Lupu
authors.forename: Carla
authors.initials: C
authors.lastname: Weinheimer
authors.forename: Attila
authors.initials: A
authors.lastname: Kovacs
authors.forename: Michael
authors.initials: M
authors.lastname: Courtois
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Muslin
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control; D019332:Endothelin-1 / Q000494:pharmacology; D006321:Heart / Q000254:growth & development*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics; D014176:Protein Biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction; D013550:Swimming
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains