title: Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy.
abstract: BACKGROUND
  In response to mechanical and pathological stress, adult mammalian hearts often undergo mal-remodeling, a process commonly characterized as pathological hypertrophy, which is associated with upregulation of fetal genes, increased fibrosis, and reduction of cardiac dysfunction. The molecular pathways that regulate this process are not fully understood.
  
  
  OBJECTIVE
  To explore the function of microRNA-155 (miR-155) in cardiac hypertrophy and remodeling.
  
  
  RESULTS
  Our previous work identified miR-155 as a critical microRNA that repressed the expression and function of the myocyte enhancer factor 2A. In this study, we found that miR-155 is expressed in cardiomyocytes and that its expression is reduced in pressure overload-induced hypertrophic hearts. In mouse models of cardiac hypertrophy, miR-155 null hearts suppressed cardiac hypertrophy and cardiac remodeling in response to 2 independent pathological stressors, transverse aortic restriction and an activated calcineurin transgene. Most importantly, loss of miR-155 prevents the progress of heart failure and substantially extends the survival of calcineurin transgenic mice. The function of miR-155 in hypertrophy is confirmed in isolated cardiomyocytes. We identified jumonji, AT rich interactive domain 2 (Jarid2) as an miR-155 target in the heart. miR-155 directly represses Jarid2, whose expression is increased in miR-155 null hearts. Inhibition of endogenous Jarid2 partially rescues the effect of miR-155 loss in isolated cardiomyocytes.
  
  
  CONCLUSIONS
  Our studies uncover miR-155 as an inducer of pathological cardiomyocyte hypertrophy and suggest that inhibition of endogenous miR-155 might have clinical potential to suppress cardiac hypertrophy and heart failure.
authors.affiliation: From the Department of Cardiology, Boston Children's Hospital, Harvard Medical School, MA (H.Y.S., J.C., M.K., Z.-P.H., J.D., J.Y., X.H., D.-Z.W.); Program of Integrative Medicine, Department of Cardiology, Beijing University of Chinese Medicine, Beijing, China (J.Y.); and Harvard Stem Cell Institute, Harvard University, Cambridge, MA (D.-Z.W.).
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Seok
authors.forename: Jinghai
authors.initials: J
authors.lastname: Chen
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kataoka
authors.forename: Zhan-Peng
authors.initials: ZP
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Jinglu
authors.initials: J
authors.lastname: Yan
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Hu
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse
keywords: Jarid2; cardiac hypertrophy; cardiomyocyte; heart failure; miR-155; microRNA; post-transcriptional regulation