title: MicroRNA-22 downregulation by atorvastatin in a mouse model of cardiac hypertrophy: a new mechanism for antihypertrophic intervention.
abstract: BACKGROUND
  Growing evidence shows that microRNAs (miRNAs) are involved in various cardiac processes including cardiac hypertrophy. However, the modulation of miRNA by pharmacological intervention in cardiomyocyte hypertrophy has not been disclosed yet. methods: We constructed neonatal rat cardiomyocyte hypertrophy induced by angiotensin II stimulation and subjected to cardiomyocyte immunochemistry, qRT-PCR and immunoblotting analysis. In addition, we constructed the mouse cardiac hypertrophy using angomir-22 stimulation and demonstrated the potential antihypertrophic mechnism of atorvastatin.
  
  
  RESULTS
  The results showed that a collection of miRNAs were aberrantly expressed in hypertrophic cardiomyocytes induced by angiotensin II stimulation. In addition, overexpression of miR-22 was found in angiotensin II-induced hypertrophic cardiomyocytes, whereas administration of atorvastatin could reverse the upregulation of miRNA-22 nearly back to the control level. Furthermore, up-regulation of miRNA-22 in cardiomyocytes in vitro and in vivo could induce cardiac hypertrophy, which could suppress the protein level of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Concomitantly, the production of ANP, BNP and β-MHC was enhanced and cardiomyocyte size was increased. However, atorvastatin could markedly knockdown miRNA-22 expression and reverse these changes in cardiomyocytes. These results suggest that the contribution of atrovastatin to cardiomyocyte hypertrophy may be involved in downregulation of miRNA-22 expression, which modulates the activity of PTEN in cardiomyocyte hypertrophy. conclusion: This study demonstrates for the first time the modulation of miRNA-22 can be achieved by pharmacological intervention. The data generated from this study provides a rationale for the development of miRNA-based strategies for antihypertrophic treatment.
authors.affiliation: Department of Radiology, the Fourth Hospital of Harbin Medical University, 31 Yinhang Street, Nangang District, Harbin, Heilongjiang, PR China.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Tu
authors.forename: Lin
authors.initials: L
authors.lastname: Wan
authors.forename: Lihong
authors.initials: L
authors.lastname: Bu
authors.forename: Dongliang
authors.initials: D
authors.lastname: Zhao
authors.forename: Dandan
authors.initials: D
authors.lastname: Dong
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.forename: Baozhong
authors.initials: B
authors.lastname: Shen
mesh_terms: D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009206:Myocardium / 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; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D035683:MicroRNAs; C574876:Mirn22 microRNA, mouse; C551613:Myh7 protein, mouse; D016376:Oligonucleotides, Antisense; D011758:Pyrroles; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D000069059:Atorvastatin; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; D018995:Myosin Heavy Chains