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Accumulative data suggest that <jats:italic>zfp91<\/jats:italic> may be an important gene to regulate all aspects of human response. However, there are no data to date about the function of <jats:italic>zfp91<\/jats:italic> on cardiac homeostasis. Thus, we aimed to observe the role of <jats:italic>zfp91<\/jats:italic> gene in mouse cardiomyocytes on myocardial homeostasis and related mechanisms under pressure overload. In the study, <jats:italic>zfp91<\/jats:italic> mRNA and protein levels were significantly reduced in TAC\u2010operated WT mice as compared with controls. Genetic ablation of <jats:italic>zfp91<\/jats:italic> dramatically led to pathological cardiac dysfunction and hypertrophy after transverse aortic constriction (TAC). Adenosine A1 receptor (Adora1) mRNA and protein expressions were significantly down\u2010regulated in the heart of <jats:italic>zfp91<\/jats:italic>\u2010deletion mice with TAC. Zfp91 overexpression reversed isoproterenol\u2010induced cardiomyocyte hypertrophy, which was abolished by selective Adora1 antagonist. Dual\u2010luciferase reporter and ChIP\u2010qPCR assays indicated that zfp91 acted on Adora1 promoter through its binding site. Last, Adora1 agonist rescued heart dysfunction and cardiac hypertrophy in z<jats:italic>fp91<\/jats:italic> loss mice after TAC. Zfp91 may transcriptionally regulate Adora1 expression in the heart, which mainly maintained cardiac homeostasis under pressure overload status. It will provide a new approach to treat cardiac hypertrophy.<\/jats:p>","DOI":"10.1111\/jcmm.15630","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T08:30:37Z","timestamp":1594974637000},"page":"10189-10201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Zinc finger protein 91 loss induces cardiac hypertrophy through adenosine A1 receptor down\u2010regulation under pressure overload status"],"prefix":"10.1111","volume":"24","author":[{"given":"Xiangqi","family":"Wu","sequence":"first","affiliation":[{"name":"Division of Cardiology Nanjing First Hospital Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"You","sequence":"additional","affiliation":[{"name":"Division of Cardiology Nanjing First Hospital Nanjing Medical University  Nanjing 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