title: Long noncoding RNA Chast promotes cardiac remodeling.
abstract: Recent studies highlighted long noncoding RNAs (lncRNAs) to play an important role in cardiac development. However, understanding of lncRNAs in cardiac diseases is still limited. Global lncRNA expression profiling indicated that several lncRNA transcripts are deregulated during pressure overload-induced cardiac hypertrophy in mice. Using stringent selection criteria, we identified Chast (cardiac hypertrophy-associated transcript) as a potential lncRNA candidate that influences cardiomyocyte hypertrophy. Cell fractionation experiments indicated that Chast is specifically up-regulated in cardiomyocytes in vivo in transverse aortic constriction (TAC)-operated mice. In accordance, CHAST homolog in humans was significantly up-regulated in hypertrophic heart tissue from aortic stenosis patients and in human embryonic stem cell-derived cardiomyocytes upon hypertrophic stimuli. Viral-based overexpression of Chast was sufficient to induce cardiomyocyte hypertrophy in vitro and in vivo. GapmeR-mediated silencing of Chast both prevented and attenuated TAC-induced pathological cardiac remodeling with no early signs on toxicological side effects. Mechanistically, Chast negatively regulated Pleckstrin homology domain-containing protein family M member 1 (opposite strand of Chast), impeding cardiomyocyte autophagy and driving hypertrophy. These results indicate that Chast can be a potential target to prevent cardiac remodeling and highlight a general role of lncRNAs in heart diseases.
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany. Excellence Cluster REBIRTH, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Janika
authors.initials: J
authors.lastname: Viereck
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Regalla
authors.initials: R
authors.lastname: Kumarswamy
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Ariana
authors.initials: A
authors.lastname: Foinquinos
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Ke
authors.initials: K
authors.lastname: Xiao
authors.affiliation: Institute of Pharmacology and Toxicology, Technical University of Munich, D-80802 Munich, Germany. German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, D-80802 Munich, Germany.
authors.forename: Petros
authors.initials: P
authors.lastname: Avramopoulos
authors.affiliation: Department of Bioinformatics, University of Würzburg, D-97074 Würzburg, Germany.
authors.forename: Meik
authors.initials: M
authors.lastname: Kunz
authors.affiliation: Department of Bioinformatics, University of Würzburg, D-97074 Würzburg, Germany. Institute of Human Genetics, University of Würzburg, D-97074 Würzburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dittrich
authors.affiliation: Institute of Experimental Hematology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Maetzig
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Zimmer
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Janet
authors.initials: J
authors.lastname: Remke
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Just
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Fendrich
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Scherf
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Bolesani
authors.affiliation: Institute of Experimental Hematology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.affiliation: Department of Cardiology, Julius-Maximilians University, D-97080 Würzburg, Germany. Comprehensive Heart Failure Center, University of Würzburg, D-97078 Würzburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.affiliation: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Zweigerdt
authors.affiliation: Department of Cardiology, Maastricht University, 6202 AZ Maastricht, Netherlands.
authors.forename: Leon J
authors.initials: LJ
authors.lastname: de Windt
authors.affiliation: Institute of Pharmacology and Toxicology, Technical University of Munich, D-80802 Munich, Germany. German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, D-80802 Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Engelhardt
authors.affiliation: Department of Bioinformatics, University of Würzburg, D-97074 Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dandekar
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Sandor
authors.initials: S
authors.lastname: Batkai
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, D-30625 Hannover, Germany. Excellence Cluster REBIRTH, Hannover Medical School, D-30625 Hannover, Germany. National Heart and Lung Institute, Imperial College London, SW3 6NP London, UK. thum.thomas@mh-hannover.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
mesh_terms: D000818:Animals; D001483:Base Sequence; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D050778:NFATC Transcription Factors / Q000378:metabolism; D011312:Pressure; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D057170:Translational Research, Biomedical; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D050778:NFATC Transcription Factors; D062085:RNA, Long Noncoding; C000612148:long non-coding RNA Chast, mouse