title: Altered melusin expression in the hearts of aortic stenosis patients.
abstract: BACKGROUND
  The role of melusin, a necessary component in pressure-induced left-ventricular hypertrophy (LVH) in mice, has not yet been determined in human cardiac hypertrophy. We analyzed for the first time the expression and regional distribution of melusin in human LVH due to aortic stenosis (AS) and determined AKT phosphorylation as a potential downstream effector of melusin signalling.
  
  
  METHODS
  Regional distribution of melusin was evaluated in four normal hearts. Melusin staining, gene expression and protein content were assessed in biopsies from normal and diseased hearts and melusin gene expression was correlated with LV functional changes. The pAKT/AKT ratio was determined in parallel and correlated with melusin protein content.
  
  
  RESULTS
  In normal hearts, melusin was found in the myocytes with a uniform regional distribution. Melusin staining, mRNA and protein were significantly decreased in human AS hearts. The reduction in melusin mRNA was significantly correlated with LVEF, LVEDD and LVESD. pAKT/AKT ratio was significantly decreased in human AS and was correlated with melusin content.
  
  
  CONCLUSIONS
  Reduction in melusin expression parallels the functional cardiac impairment in human AS. The simultaneous decrease of melusin and AKT phosphorylation suggests a connection between the loss of melusin and the decrease in systolic function.
authors.affiliation: Center for Gender in Medicine and Cardiovascular Research Center, Charité Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brokat
authors.forename: Jenny
authors.initials: J
authors.lastname: Thomas
authors.forename: Lars R
authors.initials: LR
authors.lastname: Herda
authors.forename: Christoph
authors.initials: C
authors.lastname: Knosalla
authors.forename: Reinhard
authors.initials: R
authors.lastname: Pregla
authors.forename: Mara
authors.initials: M
authors.lastname: Brancaccio
authors.forename: Federica
authors.initials: F
authors.lastname: Accornero
authors.forename: Guido
authors.initials: G
authors.lastname: Tarone
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D001706:Biopsy; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009206:Myocardium / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D012016:Reference Values; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000235:genetics / Q000473:pathology
chemical_list: D003598:Cytoskeletal Proteins; C122158:Itgb1bp2 protein, mouse; D009124:Muscle Proteins; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt