Open AccessReversible Treatment of Pressure Overload‐Induced Left Ventricular Hypertrophy through Drd5 Nucleic Acid Delivery Mediated by Functional Polyaminoglycoside
Author(s) -
Jiang Xiaoliang,
Shao Meiyu,
Liu Xue,
Liu Xing,
Zhang Xu,
Wang Yuming,
Yin Kunlun,
Wang Shuiyun,
Hu Yang,
Jose Pedro A,
Zhou Zhou,
Xu FuJian,
Yang Zhiwei
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202003706
Subject(s) - heart failure , muscle hypertrophy , left ventricular hypertrophy , medicine , cardiology , pressure overload , fibrosis , ventricle , myocardial fibrosis , cardiomyopathy , ventricular remodeling , concentric hypertrophy , ventricular hypertrophy , endocrinology , blood pressure , cardiac hypertrophy
Left ventricular hypertrophy and fibrosis are major risk factors for heart failure, which require timely and effective treatment. 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‐induced left ventricular hypertrophy. Then, a reversible treatment of left ventricular hypertrophy with Drd5 nucleic acids delivered by tobramycin‐based hyperbranched polyaminoglycoside (SS‐HPT) is studied. The heart‐specific increase in D5R expression by SS‐HPT/ Drd5 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. By contrast, SS‐HPT/ Drd5 siRNA promotes the progression of left ventricular hypertrophy and accelerates the deterioration of myocardial function into heart failure. The reduction in cardiac D5R expression and dysregulated autophagy are observed in patients with hypertrophic cardiomyopathy and heart failure. The data show a cardiac‐specific beneficial effect of SS‐HPT/ Drd5 plasmid on myocardial remodeling and dysfunction, which may provide an effective therapy of patients with left ventricular hypertrophy and heart failure.