Altered melusin expression in the hearts of aortic stenosis patients.
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.
Brokat
Sebastian
S
Center for Gender in Medicine and Cardiovascular Research Center, Charité Berlin, Germany.
Thomas
Jenny
J
Herda
Lars R
LR
Knosalla
Christoph
C
Pregla
Reinhard
R
Brancaccio
Mara
M
Accornero
Federica
F
Tarone
Guido
G
Hetzer
Roland
R
Regitz-Zagrosek
Vera
V
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
D003598:Cytoskeletal Proteins; C122158:Itgb1bp2 protein, mouse; D009124:Muscle Proteins; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt