Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy

Hee Young Seok, Jinghai Chen, Masaharu Kataoka, Zhan Peng Huang, Jian Ding, Jinglu Yan, Xiaoyun Hu, Da Zhi Wang

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

RATIONALE:: 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. METHODS AND 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.

Original languageEnglish
Pages (from-to)1585-1595
Number of pages11
JournalCirculation research
Volume114
Issue number10
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Fingerprint

Cardiomegaly
MicroRNAs
Cardiac Myocytes
Hypertrophy
Heart Failure
Calcineurin
MEF2 Transcription Factors
Mechanical Stress
Transgenes
Transgenic Mice
Fibrosis
Up-Regulation

Keywords

  • Cardiac hypertrophy
  • Cardiomyocyte
  • Heart failure
  • Jarid2
  • microRNA
  • miR-155
  • Post-transcriptional regulation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Seok, H. Y., Chen, J., Kataoka, M., Huang, Z. P., Ding, J., Yan, J., ... Wang, D. Z. (2014). Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy. Circulation research, 114(10), 1585-1595. https://doi.org/10.1161/CIRCRESAHA.114.303784

Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy. / Seok, Hee Young; Chen, Jinghai; Kataoka, Masaharu; Huang, Zhan Peng; Ding, Jian; Yan, Jinglu; Hu, Xiaoyun; Wang, Da Zhi.

In: Circulation research, Vol. 114, No. 10, 01.01.2014, p. 1585-1595.

Research output: Contribution to journalArticle

Seok, HY, Chen, J, Kataoka, M, Huang, ZP, Ding, J, Yan, J, Hu, X & Wang, DZ 2014, 'Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy', Circulation research, vol. 114, no. 10, pp. 1585-1595. https://doi.org/10.1161/CIRCRESAHA.114.303784
Seok, Hee Young ; Chen, Jinghai ; Kataoka, Masaharu ; Huang, Zhan Peng ; Ding, Jian ; Yan, Jinglu ; Hu, Xiaoyun ; Wang, Da Zhi. / Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy. In: Circulation research. 2014 ; Vol. 114, No. 10. pp. 1585-1595.
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