Correlation Engine 2.0
Clear Search sequence regions

Sizes of these terms reflect their relevance to your search.

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.


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. AAV-mediated expression of NFAT decoy oligonucleotides protects from cardiac hypertrophy and heart failure. Basic research in cardiology. 2021 Jun 04;116(1):38

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 34089101

View Full Text