title: MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress.
abstract: BACKGROUND
  The adult heart is composed primarily of terminally differentiated, mature cardiomyocytes that express signature genes related to contraction. In response to mechanical or pathological stress, the heart undergoes hypertrophic growth, a process defined as an increase in cardiomyocyte cell size without an increase in cell number. However, the molecular mechanism of cardiac hypertrophy is not fully understood.
  
  
  OBJECTIVE
  To identify and characterize microRNAs that regulate cardiac hypertrophy and remodeling.
  
  
  RESULTS
  Screening for muscle-expressed microRNAs that are dynamically regulated during muscle differentiation and hypertrophy identified microRNA-22 (miR-22) as a cardiac- and skeletal muscle-enriched microRNA that is upregulated during myocyte differentiation and cardiomyocyte hypertrophy. Overexpression of miR-22 was sufficient to induce cardiomyocyte hypertrophy. We generated mouse models with global and cardiac-specific miR-22 deletion, and we found that cardiac miR-22 was essential for hypertrophic cardiac growth in response to stress. miR-22-null hearts blunted cardiac hypertrophy and cardiac remodeling in response to 2 independent stressors: isoproterenol infusion and an activated calcineurin transgene. Loss of miR-22 sensitized mice to the development of dilated cardiomyopathy under stress conditions. We identified Sirt1 and Hdac4 as miR-22 targets in the heart.
  
  
  CONCLUSIONS
  Our studies uncover miR-22 as a critical regulator of cardiomyocyte hypertrophy and cardiac remodeling.
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Zhan-Peng
authors.initials: ZP
authors.lastname: Huang
authors.forename: Jinghai
authors.initials: J
authors.lastname: Chen
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Seok
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kataoka
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Hu
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D017930:Genes, Reporter; D057809:HEK293 Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D056564:Sirtuin 1 / Q000378:metabolism; D014162:Transfection; D020257:Ventricular Remodeling
chemical_list: C580892:MIRN22 microRNA, rat; D035683:MicroRNAs; C574876:Mirn22 microRNA, mouse; D019703:Calcineurin; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; C559944:HDAC4 protein, rat; D006655:Histone Deacetylases; D007545:Isoproterenol