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SHR Neuro Krebs Kardio Lipid

Ljubojevic, S; Radulovic, S; Leitinger, G; Sedej, S; Sacherer, M; Holzer, M; Winkler, C; Pritz, E; Mittler, T; Schmidt, A; Sereinigg, M; Wakula, P; Zissimopoulos, S; Bisping, E; Post, H; Marsche, G; Bossuyt, J; Bers, DM; Kockskämper, J; Pieske, B.
Early remodeling of perinuclear Ca2+ stores and nucleoplasmic Ca2+ signaling during the development of hypertrophy and heart failure.
Circulation. 2014; 130(3):244-255 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bisping Egbert
Holzer Michael
Holzer Senka
Leitinger Gerd
Marsche Gunther
Pieske Burkert Mathias
Post Heiner
Pritz Elisabeth
Radulovic Snjezana
Sacherer Michael
Schmidt Albrecht
Sedej Simon
Sereinigg Michael
Wakula-Heinzel Paulina
Winkler Claudia
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Number of Figures: 8
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Abstract:
A hallmark of heart failure is impaired cytoplasmic Ca(2+) handling of cardiomyocytes. It remains unknown whether specific alterations in nuclear Ca(2+) handling via altered excitation-transcription coupling contribute to the development and progression of heart failure. Using tissue and isolated cardiomyocytes from nonfailing and failing human hearts, as well as mouse and rabbit models of hypertrophy and heart failure, we provide compelling evidence for structural and functional changes of the nuclear envelope and nuclear Ca(2+) handling in cardiomyocytes as remodeling progresses. Increased nuclear size and less frequent intrusions of the nuclear envelope into the nuclear lumen indicated altered nuclear structure that could have functional consequences. In the (peri)nuclear compartment, there was also reduced expression of Ca(2+) pumps and ryanodine receptors, increased expression of inositol-1,4,5-trisphosphate receptors, and differential orientation among these Ca(2+) transporters. These changes were associated with altered nucleoplasmic Ca(2+) handling in cardiomyocytes from hypertrophied and failing hearts, reflected as increased diastolic Ca(2+) levels with diminished and prolonged nuclear Ca(2+) transients and slowed intranuclear Ca(2+) diffusion. Altered nucleoplasmic Ca(2+) levels were translated to higher activation of nuclear Ca(2+)/calmodulin-dependent protein kinase II and nuclear export of histone deacetylases. Importantly, the nuclear Ca(2+) alterations occurred early during hypertrophy and preceded the cytoplasmic Ca(2+) changes that are typical of heart failure. During cardiac remodeling, early changes of cardiomyocyte nuclei cause altered nuclear Ca(2+) signaling implicated in hypertrophic gene program activation. Normalization of nuclear Ca(2+) regulation may therefore be a novel therapeutic approach to prevent adverse cardiac remodeling. © 2014 American Heart Association, Inc.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Calcium - metabolism
Calcium Signaling - physiology
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
Cardiomegaly - metabolism Cardiomegaly - pathology Cardiomegaly - physiopathology
Cell Nucleus - metabolism
Disease Models, Animal -
Electric Stimulation -
Female -
Heart Failure - metabolism Heart Failure - pathology Heart Failure - physiopathology
Histone Deacetylases - metabolism
Humans -
Inositol 1,4,5-Trisphosphate Receptors - metabolism
Male -
Mice -
Mice, Inbred C57BL -
Middle Aged -
Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology
Rabbits -
Ventricular Remodeling - physiology

Find related publications in this database (Keywords)
calcium signaling
heart failure
nuclear envelope
remodeling
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