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. 2024 Jun;18(3):484-498.
doi: 10.1007/s11684-023-1036-4. Epub 2024 May 14.

lncRNA ZNF593-AS inhibits cardiac hypertrophy and myocardial remodeling by upregulating Mfn2 expression

Xiang Nie #  1   2 , Jiahui Fan #  1   2 , Yanwen Wang  1   2 , Rong Xie  1   2 , Chen Chen  1   2 , Huaping Li  3   4 , Dao Wen Wang  5   6
Affiliations

lncRNA ZNF593-AS inhibits cardiac hypertrophy and myocardial remodeling by upregulating Mfn2 expression

Xiang Nie et al. Front Med. 2024 Jun.

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.

Keywords: Mfn2; ZNF593-AS; cardiac hypertrophy; lncRNA; oxidative phosphorylation.

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References

    1. Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol 2018; 15(7): 387–407 - PubMed - DOI
    1. Oldfield CJ, Duhamel TA, Dhalla NS. Mechanisms for the transition from physiological to pathological cardiac hypertrophy. Can J Physiol Pharmacol 2020; 98(2): 74–84 - PubMed - DOI
    1. Dorn GW2nd, Vega RB, Kelly DP. Mitochondrial biogenesis and dynamics in the developing and diseased heart. Genes Dev 2015; 29(19): 1981–1991 - PubMed - PMC - DOI
    1. Woodall BP, Gustafsson AB. Autophagy—a key pathway for cardiac health and longevity. Acta Physiol (Oxf) 2018; 223(4): e13074 - PubMed - DOI
    1. Chen L, Liu B, Qin Y, Li A, Gao M, Liu H, Gong G. Mitochondrial fusion protein Mfn2 and its role in heart failure. Front Mol Biosci 2021; 8: 681237 - PubMed - PMC - DOI

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