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AAV-mediated expression of NFAT decoy oligonucleotides protects from cardiac hypertrophy and heart failure

Previous studies have underlined the substantial role of nuclear factor of activated T cells (NFAT) in hypertension-induced myocardial hypertrophy ultimately leading to heart failure. Here, we aimed at neutralizing four members of the NFAT family of transcription factors as a therapeutic strategy fo...

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Hauptverfasser: Remes, Anca (VerfasserIn) , Wagner, Andreas H. (VerfasserIn) , Schmiedel, Nesrin (VerfasserIn) , Heckmann, Markus B. (VerfasserIn) , Ruf, Theresa (VerfasserIn) , Ding, Lin (VerfasserIn) , Jungmann, Andreas (VerfasserIn) , Senger, Frauke (VerfasserIn) , Katus, Hugo (VerfasserIn) , Ullrich, Nina D. (VerfasserIn) , Frey, Norbert (VerfasserIn) , Hecker, Markus (VerfasserIn) , Müller, Oliver J. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 04 June 2021
In: Basic research in cardiology
Year: 2021, Jahrgang: 116, Pages: 1-12
ISSN:1435-1803
DOI:10.1007/s00395-021-00880-w
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s00395-021-00880-w
Verlag, lizenzpflichtig, Volltext: https://link.springer.com/article/10.1007%2Fs00395-021-00880-w
Volltext
Verfasserangaben:Anca Remes, Andreas H. Wagner, Nesrin Schmiedel, Markus Heckmann, Theresa Ruf, Lin Ding, Andreas Jungmann, Frauke Senger, Hugo A. Katus, Nina D. Ullrich, Norbert Frey, Markus Hecker, Oliver J. Müller
Beschreibung
Zusammenfassung:Previous studies have underlined the substantial role of nuclear factor of activated T cells (NFAT) in hypertension-induced myocardial hypertrophy ultimately leading to heart failure. Here, we aimed at neutralizing four members of the NFAT family of transcription factors as a therapeutic strategy for myocardial hypertrophy transiting to heart failure through AAV-mediated cardiac expression of a RNA-based decoy oligonucleotide (dON) targeting NFATc1-c4. AAV-mediated dON expression markedly decreased endothelin-1 induced cardiomyocyte hypertrophy in vitro and resulted in efficient expression of these dONs in the heart of adult mice as evidenced by fluorescent in situ hybridization. Cardiomyocyte-specific dON expression both before and after induction of transverse aortic constriction protected mice from development of cardiac hypertrophy, cardiac remodeling, and heart failure. Singular systemic administration of AAVs enabling a cell-specific expression of dONs for selective neutralization of a given transcription factor may thus represent a novel and powerful therapeutic approach.
Beschreibung:Gesehen am 04.11.2021
Beschreibung:Online Resource
ISSN:1435-1803
DOI:10.1007/s00395-021-00880-w

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