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The neonatal rat cardiomyocytes, H9C2, and HEK293 cells were used to determine the mechanistic role of miR\u2010204.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The stretch induces miR\u2010204 expression, and miR\u2010204 inhibits the stretch\u2010induced hypertrophic response of H9C2 cells. The mice lacking miR\u2010204 displayed a higher susceptibility to CH\/CD during pressure overload, which was reversed by the adeno\u2010associated virus serotype\u20109\u2010mediated cardioselective miR\u2010204 overexpression. Bioinformatic analysis of the cardiac transcriptomics of miR\u2010204 knockout mice following pressure overload suggested deregulation of apelin\u2010receptor (APJ) signalling. We found that the stretch\u2010induced extracellular signal\u2010regulated kinase 1\/2 (ERK1\/2) activation and hypertrophy\u2010related genes expression depend on the APJ, and both of these effects are subject to miR\u2010204 levels. The dynamin inhibitor dynasore inhibited both stretch\u2010induced APJ endocytosis and ERK1\/2 activation. In contrast, the miR\u2010204\u2010induced APJ endocytosis was neither inhibited by dynamin inhibitors (dynasore and dyngo) nor associated with ERK1\/2 activation. We find that the miR\u2010204 increases the expression of ras\u2010associated binding proteins (e.g., Rab5a, Rab7) that regulate cellular endocytosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results show that miR\u2010204 regulates trafficking of APJ and confers resistance to pressure overload\u2010induced CH\/CD, and boosting miR\u2010204 can inhibit the development of CH\/CD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.693","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T08:59:54Z","timestamp":1642755594000},"source":"Crossref","is-referenced-by-count":13,"title":["The microRNA\u2010204\u20105p inhibits APJ signalling and confers resistance to cardiac hypertrophy and dysfunction"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-5082","authenticated-orcid":false,"given":"Ravinder Reddy","family":"Gaddam","sequence":"first","affiliation":[{"name":"Department of 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Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamsitha","family":"Shankaiahgari","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"London","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Carver College of Medicine University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaikobad","family":"Irani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Carver College of Medicine University of Iowa  Iowa City Iowa 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