title: Qiliqiangxin Attenuates Phenylephrine-Induced Cardiac Hypertrophy through Downregulation of MiR-199a-5p.
abstract: OBJECTIVE
  Qiliqiangxin (QL), a traditional Chinese medicine, has long been used to treat chronic heart failure. Previous studies demonstrated that QL could prevent cardiac remodeling and hypertrophy in response to hypertensive or ischemic stress. However, little is known about whether QL could modulate cardiac hypertrophy in vitro, and (if so) whether it is through modulation of specific hypertrophy-related microRNA.
  
  
  METHODS
  The primary neonatal rat ventricular cardiomyocytes were isolated, cultured, and treated with phenylephrine (PE, 50 µmol/L, 48 h) to induce hypertrophy in vitro, in the presence or absence of pretreatment with QL (0.5 µg/ml, 48 h). The cell surface area was determined by immunofluorescent staining for α-actinin. The mRNA levels of hypertrophic markers including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (MYH7) were assayed by qRT-PCRs. The protein synthesis of cardiomyocytes was determined by the protein/DNA ratio. The miR-199a-5p expression level was quantified in PE-treated cardiomyocytes and heart samples from acute myocardial infarction (AMI) mouse model. MiR-199a-5p overexpression was used to determine its role in the anti-hypertrophic effect of QL on cardiomyocytes.
  
  
  RESULTS
  PE induced obvious enlargement of cell surface in cardiomyocytes, paralleling with increased ANP, BNP, and MYH7 mRNA levels and elevated protein/DNA ratio. All these changes were reversed by the treatment with QL. Meanwhile, miR-199a-5p was increased in AMI mouse heart tissues. Of note, the increase of miR-199a-5p in PE-treated cardiomyocytes was reversed by the treatment with QL. Moreover, overexpression of miR-199a-5p abolished the anti-hypertrophic effect of QL on cardiomyocytes.
  
  
  CONCLUSIONS
  QL prevents PE-induced cardiac hypertrophy. MiR-199a-5p is increased in cardiac hypertrophy, while reduced by treatment with QL. miR-199a-5p suppression is essential for the anti-hypertrophic effect of QL on cardiomyocytes.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.forename: Qiulian
authors.initials: Q
authors.lastname: Zhou
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.forename: Shutong
authors.initials: S
authors.lastname: Shen
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yihua
authors.initials: Y
authors.lastname: Bei
authors.forename: Xinli
authors.initials: X
authors.lastname: Li
mesh_terms: D000185:Actinin / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D008516:Medicine, Chinese Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010656:Phenylephrine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004365:Drugs, Chinese Herbal; C000594638:MYH7 protein, rat; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; C572413:qiliqiangxin; D000185:Actinin; D020097:Natriuretic Peptide, Brain; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D018995:Myosin Heavy Chains