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: | , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
04 June 2021
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| 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 
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| 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 |
MARC
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| 520 | |a 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. | ||
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