Early Remodeling of Perinuclear Ca <sup>2+</sup> Stores and Nucleoplasmic Ca <sup>2+</sup> Signaling During the Development of Hypertrophy and Heart Failure
-
- Senka Ljubojevic
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Snjezana Radulovic
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Gerd Leitinger
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Simon Sedej
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Michael Sacherer
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Michael Holzer
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Claudia Winkler
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Elisabeth Pritz
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Tobias Mittler
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Albrecht Schmidt
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Michael Sereinigg
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Paulina Wakula
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Spyros Zissimopoulos
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Egbert Bisping
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Heiner Post
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Gunther Marsche
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Julie Bossuyt
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Donald M. Bers
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Jens Kockskämper
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
-
- Burkert Pieske
- From the Department of Cardiology (S.L., S.R., S.S., M. Sacherer, C.W., T.M., A.S., P.W., E.B., H.P., B.P.), Institute of Cell Biology, Histology and Embryology (G.L., E.P.), Institute of Experimental and Clinical Pharmacology (M.H., G.M.), and Division of Transplantation Surgery (M. Sereinigg), Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Translational Heart Failure Research, Graz, Austria (S.L., S.S., P.W., E.B., B.P.); Department of Pharmacology, University of...
抄録
<jats:sec> <jats:title>Background—</jats:title> <jats:p> A hallmark of heart failure is impaired cytoplasmic Ca <jats:sup>2+</jats:sup> handling of cardiomyocytes. It remains unknown whether specific alterations in nuclear Ca <jats:sup>2+</jats:sup> handling via altered excitation-transcription coupling contribute to the development and progression of heart failure. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> 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 <jats:sup>2+</jats:sup> 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 <jats:sup>2+</jats:sup> pumps and ryanodine receptors, increased expression of inositol-1,4,5-trisphosphate receptors, and differential orientation among these Ca <jats:sup>2+</jats:sup> transporters. These changes were associated with altered nucleoplasmic Ca <jats:sup>2+</jats:sup> handling in cardiomyocytes from hypertrophied and failing hearts, reflected as increased diastolic Ca <jats:sup>2+</jats:sup> levels with diminished and prolonged nuclear Ca <jats:sup>2+</jats:sup> transients and slowed intranuclear Ca <jats:sup>2+</jats:sup> diffusion. Altered nucleoplasmic Ca <jats:sup>2+</jats:sup> levels were translated to higher activation of nuclear Ca <jats:sup>2+</jats:sup> /calmodulin-dependent protein kinase II and nuclear export of histone deacetylases. Importantly, the nuclear Ca <jats:sup>2+</jats:sup> alterations occurred early during hypertrophy and preceded the cytoplasmic Ca <jats:sup>2+</jats:sup> changes that are typical of heart failure. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p> During cardiac remodeling, early changes of cardiomyocyte nuclei cause altered nuclear Ca <jats:sup>2+</jats:sup> signaling implicated in hypertrophic gene program activation. Normalization of nuclear Ca <jats:sup>2+</jats:sup> regulation may therefore be a novel therapeutic approach to prevent adverse cardiac remodeling. </jats:p> </jats:sec>
収録刊行物
-
- Circulation
-
Circulation 130 (3), 244-255, 2014-07-15
Ovid Technologies (Wolters Kluwer Health)