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

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

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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.

lncRNAZNF593-AScardiac hypertrophyMfn2oxidative phosphorylation

Xiang Nie、Jiahui Fan、Yanwen Wang、Rong Xie、Chen Chen、Huaping Li、Dao Wen Wang

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Division of Cardiology,Department of Internal Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders,Wuhan 430030,China

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaChina Postdoctoral Science Foundation

8210039982100400817906242021M701315

2024

10.1007/s11684-023-1036-4

医学前沿
高等教育出版社

医学前沿

CSTPCD
影响因子：1.362
ISSN：2095-0217
年,卷(期)：2024.18(3)