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Altered melusin expression in the hearts of aortic stenosis patients
Author(s) -
Brokat Sebastian,
Thomas Jenny,
Herda Lars R.,
Knosalla Christoph,
Pregla Reinhard,
Brancaccio Mara,
Accornero Federica,
Tarone Guido,
Hetzer Roland,
RegitzZagrosek Vera
Publication year - 2007
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2007.02.009
Subject(s) - ejection fraction , medicine , muscle hypertrophy , protein kinase b , phosphorylation , cardiology , pi3k/akt/mtor pathway , heart failure , distribution (mathematics) , messenger rna , stenosis , myocyte , endocrinology , signal transduction , gene , microbiology and biotechnology , biology , biochemistry , mathematical analysis , mathematics
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. Conclusion: 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.