title: Overexpression of microRNA-99a Attenuates Cardiac Hypertrophy.
abstract: Pathological cardiomyocyte hypertrophy is associated with significantly increased risk of heart failure, one of the leading medical causes of mortality worldwide. MicroRNAs are known to be involved in pathological cardiac remodeling. However, whether miR-99a participates in the signaling cascade leading to cardiac hypertrophy is unknown. To evaluate the role of miR-99a in cardiac hypertrophy, we assessed the expression of miR-99a in hypertrophic cardiomyocytes induced by isoprenaline (ISO)/angiotensin-II (Ang II) and in mice model of cardiac hypertrophy induced by transverse aortic constriction (TAC). Expression of miR-99a was evaluated in these hypertrophic cells and hearts. We also found that miR-99a expression was highly correlated with cardiac function of mice with heart failure (8 weeks after TAC surgery). Overexpression of miR-99a attenuated cardiac hypertrophy in TAC mice and cellular hypertrophy in stimuli treated cardiomyocytes through down-regulation of expression of mammalian target of rapamycin (mTOR). These results indicate that miR-99a negatively regulates physiological hypertrophy through mTOR signaling pathway, which may provide a new therapeutic approach for pressure-overload heart failure.
authors.affiliation: Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: From the Department of Cardiology, Drum Tower Clinic Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Bingjian
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D049108:Cell Enlargement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism* / Q000627:therapeutic use; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C573158:Mirn99 microRNA, mouse; D000804:Angiotensin II; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D007545:Isoproterenol