Schematic overview of cell-cycle activities, global DNA methylation, and metabolic properties of fetal, neonatal, adult, and hypertrophic cardiac myocytes. Green arrows represent cell-cycle processes leading to endomitosis and multinucleation, whereas orange arrows refer to endoreduplication resulting in polyploidy. cTnI (TNNI3) indicates cardiac troponin; FAO, fatty acid oxidation; and ssTnI(TNNI1), slow skeletal troponin.
Schematic overview of the potential interplay between metabolic signals and epigenetic mechanisms for regulation of cardiac myocyte proliferation. Oxygen-dependent stimulation of mitochondrial respiration increases α-ketoglutarate (α-KG) production, which might stimulate DNA and histone demethylation thereby activating anti-proliferative genes or inducing accumulation of intracellular reactive oxygen species (ROS) and DNA damage responses. Such cues might promote polyplodization and/or activation of Hippo signaling prompting cell-cycle exit. In contrast, hypoxia stabilizes HIF1α (hypoxia-inducible factor 1-alpha) and leads to accumulation of intermediate metabolites such as succinate and fumarate, which inhibit α-KG–dependent epigenetic modifiers including TETs (ten–eleven translocation) and histone demethylases (HDMs) and stabilize HIF1α thus activating proproliferative gene programs. In addition, fumarate activates the Nrf2/Pitx2/Yap1 axis, which positively regulates proproliferative gene programs. Dashed lines indicate regulatory cascades investigated in noncardiac myocytes.
Thomas Eschenhagen, Roberto Bolli, Thomas Braun, Loren J. Field, Bernd K. Fleischmann, Jonas Frisén, Mauro Giacca, Joshua M. Hare, Steven R. Houser, Richard T. Lee, Eduardo Marbán, James F. Martin, Jeffery D. Molkentin, Charles E. Murry, Paul R. Riley, Pilar Ruiz-Lozano, Hesham A. Sadek, Mark A. Sussman and Joseph A. Hill
Circulation. 2017;CIRCULATIONAHA.117.029343, originally published July 6, 2017
Image of the new Max Planck Institute for Heart and Lung Research (MPI-HLR) research building in Bad Nauheim next to the Kerckhoff Hospital. The building was opened in spring 2010. Bottom: group photograph of the 4 department directors (from left to right, Didier Stainier, Stefan Offermanns, Werner Seeger, and Thomas Braun).
A, Organization of the Max Planck Institute for Heart and Lung Research (MPI-HLR). Main cooperation partners are shown as well. B, Numbers of employees at the MPI-HLR from 2006 until 2016. C, Numbers of publications between 2006 and 2016.
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Kuenne, Stefan Guenther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Antonella Di Stilo, Manuela Aragno, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher and Carlo Gaetano
