title: Sequential alterations in Akt, GSK3β, and calcineurin signalling in the mouse left ventricle after thoracic aortic constriction.
abstract: Left ventricular hypertrophy (LVH) is an adaptive response to chronic biomechanical stress that generally progresses to maladaptive hypertrophy and heart failure (HF). We studied the activation of protein kinase B (Akt/PKB), glycogen synthase kinase 3 beta (GSK3β), and calcineurin (Cn) at 3, 7, 15, 30, and 60 days following transverse aortic constriction (TAC) in 4-week-old mice. Following TAC, GSK3β inactivation at day 3 was associated with Akt activation, whereas at days 15 and 30, it appeared to be controlled by other kinases. Moderate nonsignificant Cn activation occurred at the early stages, and peak activation at day 30, concomitant with GSK3β inactivation and overt LVH and HF. At the latest stage (day 60), despite further progression of LVH and HF, Cn activation appeared attenuated. Early stages of LVH were associated with Ca2+-handling protein upregulation, whereas major Cn activation, associated with GSK3β inactivation, appeared to engage maladaptive hypertrophy and progression to HF associated with Ca2+-handling protein downregulation.
authors.affiliation: Inserm and Université Paris Diderot, UMR 698, 46 rue Henri Huchard, Paris, France.
authors.forename: Miresta
authors.initials: M
authors.lastname: Prévilon
authors.forename: Mylène
authors.initials: M
authors.lastname: Pezet
authors.forename: Céline
authors.initials: C
authors.lastname: Dachez
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Mercadier
authors.forename: Patricia
authors.initials: P
authors.lastname: Rouet-Benzineb
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D019703:Calcineurin / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D006333:Heart Failure / Q000209:etiology*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology*; D008297:Male; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D050778:NFATC Transcription Factors; C445503:transcription factor NF-AT c3; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D019703:Calcineurin; D002118:Calcium