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Genetic therapy has been shown to ameliorate hypertrophic cardiac damage. In this study, it is found that in mice, the dopamine D5 receptor (D5R) expression in the left ventricle (LV) progressively decreases with worsening of transverse aortic constriction\u2010induced left ventricular hypertrophy. Then, a reversible treatment of left ventricular hypertrophy with <jats:italic>Drd5<\/jats:italic> nucleic acids delivered by tobramycin\u2010based hyperbranched polyaminoglycoside (SS\u2010HPT) is studied. The heart\u2010specific increase in D5R expression by SS\u2010HPT\/<jats:italic>Drd5<\/jats:italic> plasmid in the early stage of left ventricular hypertrophy attenuates cardiac hypertrophy and fibrosis by preventing oxidative and endoplasmic reticulum (ER) stress and ameliorating autophagic dysregulation. 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The data show a cardiac\u2010specific beneficial effect of SS\u2010HPT\/<jats:italic>Drd5<\/jats:italic> plasmid on myocardial remodeling and dysfunction, which may provide an effective therapy of patients with left ventricular hypertrophy and heart failure.<\/jats:p>","DOI":"10.1002\/advs.202003706","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T02:59:57Z","timestamp":1610247597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Reversible Treatment of Pressure Overload\u2010Induced Left Ventricular Hypertrophy through <i>Drd5<\/i> Nucleic Acid Delivery Mediated by Functional Polyaminoglycoside"],"prefix":"10.1002","volume":"8","author":[{"given":"Xiaoliang","family":"Jiang","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine (The Institute of Laboratory Animal Sciences, CAMS &amp; PUMC), and Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases  5 Pan Jia Yuan Nan Li, Chaoyang District Beijing 100021 P. 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