AAV-mediated expression of NFAT decoy oligonucleotides protects from cardiac hypertrophy and heart failure.
Basic Res Cardiol
; 116(1): 38, 2021 06 04.
Article
en En
| MEDLINE
| ID: mdl-34089101
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligonucleótidos
/
Terapia Genética
/
Hipertrofia Ventricular Izquierda
/
Dependovirus
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Miocitos Cardíacos
/
Factores de Transcripción NFATC
/
Insuficiencia Cardíaca
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Basic Res Cardiol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania