lncRNA ZNF593-AS inhibits cardiac hypertrophy and myocardial remodeling by upregulating Mfn2 expression.
Front Med
; 18(3): 484-498, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38743133
ABSTRACT
lncRNA ZNF593 antisense (ZNF593-AS) transcripts have been implicated in heart failure through the regulation of myocardial contractility. The decreased transcriptional activity of ZNF593-AS has also been detected in cardiac hypertrophy. However, the function of ZNF593-AS in cardiac hypertrophy remains unclear. Herein, we report that the expression of ZNF593-AS reduced in a mouse model of left ventricular hypertrophy and cardiomyocytes in response to treatment with the hypertrophic agonist phenylephrine (PE). In vivo, ZNF593-AS aggravated pressure overload-induced cardiac hypertrophy in knockout mice. By contrast, cardiomyocyte-specific transgenic mice (ZNF593-AS MHC-Tg) exhibited attenuated TAC-induced cardiac hypertrophy. In vitro, vector-based overexpression using murine or human ZNF593-AS alleviated PE-induced myocyte hypertrophy, whereas GapmeR-induced inhibition aggravated hypertrophic phenotypes. By using RNA-seq and gene set enrichment analyses, we identified a link between ZNF593-AS and oxidative phosphorylation and found that mitofusin 2 (Mfn2) is a direct target of ZNF593-AS. ZNF593-AS exerts an antihypertrophic effect by upregulating Mfn2 expression and improving mitochondrial function. Therefore, it represents a promising therapeutic target for combating pathological cardiac remodeling.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação para Cima
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Cardiomegalia
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Miócitos Cardíacos
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RNA Longo não Codificante
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GTP Fosfo-Hidrolases
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Front Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China