title: The transcription factor GATA4 promotes myocardial regeneration in neonatal mice.
abstract: Heart failure is often the consequence of insufficient cardiac regeneration. Neonatal mice retain a certain capability of myocardial regeneration until postnatal day (P)7, although the underlying transcriptional mechanisms remain largely unknown. We demonstrate here that cardiac abundance of the transcription factor GATA4 was high at P1, but became strongly reduced at P7 in parallel with loss of regenerative capacity. Reconstitution of cardiac GATA4 levels by adenoviral gene transfer markedly improved cardiac regeneration after cryoinjury at P7. In contrast, the myocardial scar was larger in cardiomyocyte-specific Gata4 knockout (CM-G4-KO) mice after cryoinjury at P0, indicative of impaired regeneration, which was accompanied by reduced cardiomyocyte proliferation and reduced myocardial angiogenesis in CM-G4-KO mice. Cardiomyocyte proliferation was also diminished in cardiac explants from CM-G4-KO mice and in isolated cardiomyocytes with reduced GATA4 expression. Mechanistically, decreased GATA4 levels caused the downregulation of several pro-regenerative genes (among them interleukin-13, Il13) in the myocardium. Interestingly, systemic administration of IL-13 rescued defective heart regeneration in CM-G4-KO mice and could be evaluated as therapeutic strategy in the future.
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Malek Mohammadi
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Badder
authors.initials: B
authors.lastname: Kattih
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Grund
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Natali
authors.initials: N
authors.lastname: Froese
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Mortimer
authors.initials: M
authors.lastname: Korf-Klingebiel
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Gigina
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schrameck
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rudat
authors.affiliation: Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA.
authors.forename: Qiangrong
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany.|Cluster of Excellence REBIRTH, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.|Cluster of Excellence REBIRTH, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.|Cluster of Excellence REBIRTH, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany heineke.joerg@mh-hannover.de.|Cluster of Excellence REBIRTH, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Joerg
authors.identifier: 0000-0002-1541-3030
authors.initials: J
authors.lastname: Heineke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D006335:Heart Injuries; D051379:Mice; D018345:Mice, Knockout; D012038:Regeneration; D014158:Transcription, Genetic; D014161:Transduction, Genetic
chemical_list: D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse
keywords: GATA4; IL‐13; cardiac regeneration; cardiomyocyte proliferation; neonatal cryoinfarction