MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress

Zhan Peng Huang, Jinghai Chen, Hee Young Seok, Zheng Zhang, Masaharu Kataoka, Xiaoyun Hu, Da Zhi Wang

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

Rationale: 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. Methods and 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.

Original languageEnglish
Pages (from-to)1234-1243
Number of pages10
JournalCirculation research
Volume112
Issue number9
DOIs
Publication statusPublished - 2013 Apr 26

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Keywords

  • calcineurin
  • cardiac hypertrophy
  • dilated cardiomyopathy
  • heart
  • isoproterenol
  • microRNA-22
  • posttranscriptional regulation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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