Histone deacetylase inhibition by Entinostat for the prevention of electrical and structural remodeling in heart failure

BACKGROUND: The development of heart failure is accompanied by complex changes in cardiac electrophysiology and functional properties of cardiomyocytes and fibroblasts. Histone deacetylase (HDAC) inhibitors hold great promise for the pharmaceutical therapy of several malignant diseases. Here, we des...

Authors: Freundt, Johanna K.
Frommeyer, Gerrit
Spieker, Georg Tilmann
Wötzel, Fabian
Schulze Grotthoff, Jochen
Stypmann, Jörg
Hempel, Georg
Schäfers, Michael
Jacobs, Andreas H.
Eckardt, Lars
Lange, Philipp S.
Division/Institute:FB 05: Medizinische Fakultät
FB 12: Chemie und Pharmazie
Universität Münster
Document types:Article
Media types:Text
Publication date:2019
Date of publication on miami:28.02.2020
Modification date:28.02.2020
Edition statement:[Electronic ed.]
Source:BMC Pharmacology and Toxicology 20 (2019) 16, 1-9
Subjects:HDAC; Entinostat; Arrhythmias; Remodeling; Fibrosis
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Funding:Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
This work was supported by the fund “Innovative Medical Research” of the University of Münster Medical School [I-LA11123].
Format:PDF document
URN:urn:nbn:de:hbz:6-92109546463
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-92109546463
Other Identifiers:DOI: https://doi.org/10.1186/s40360-019-0294-x
Digital documents:artikel_lange_2019.pdf

BACKGROUND: The development of heart failure is accompanied by complex changes in cardiac electrophysiology and functional properties of cardiomyocytes and fibroblasts. Histone deacetylase (HDAC) inhibitors hold great promise for the pharmaceutical therapy of several malignant diseases. Here, we describe novel effects of the class I HDAC inhibitor Entinostat on electrical and structural remodeling in an in vivo model of pacing induced heart failure. METHODS: Rabbits were implanted a pacemaker system, subjected to rapid ventricular pacing and treated with Entinostat or placebo, respectively. Following stimulation, rabbit hearts were explanted and subsequently subjected to electrophysiological studies and further immunohistological analyses of left ventricles. RESULTS: In vivo, rapid ventricular stimulation caused a significant prolongation of monophasic action potential duration compared to sham hearts (from 173 ± 26 ms to 250 ± 41 ms; cycle length 900 ms; p