Effect of atorvastatin on microRNA 221 / 222 expression in endothelial progenitor cells obtained from patients with coronary artery disease

Eur J Clin Invest. 2009 May;39(5):359-67. doi: 10.1111/j.1365-2362.2009.02110.x.


Background: Endothelial progenitor cells (EPCs) play an important role in the maintenance of vascular integrity. Lipid lowering therapy (LLT) with statins may contribute to biologically relevant activities including the proliferation of endothelial cells. The physiological role of microRNA (miR)-221/222, a newly discovered class of small RNA, is closely linked to the proliferation of endothelial cells. We therefore investigated whether LLT with statins might affect miR-221/222 expression in EPCs obtained from patients with coronary artery disease (CAD).

Materials and methods: This study included 44 patients with stable CAD and 22 subjects without CAD (non-CAD). Patients with CAD were randomized to 12 months of LLT with atorvastatin (10 mg day(-1)) or pravastatin (10 mg day(-1)). EPCs were obtained from peripheral blood at baseline and after 12 months of statin therapy. Levels of miR-221/222 in EPCs were measured by real-time RT-PCR.

Results: Levels of miR-221/222 were significantly higher in the CAD group than in the non-CAD group (P < 0.01). Levels of miR-221/222 were weakly negatively correlated with EPC number in the CAD group. After 12 months of therapy, changes in lipid profiles were greater in the atorvastatin group than in the pravastatin group. LLT with atorvastatin markedly increased EPC numbers and decreased miR-221/222 levels (all P < 0.05), whereas LLT with pravastatin did not change EPC numbers or miR-221/222 levels.

Conclusions: This study demonstrates that LLT with atorvastatin increases EPC numbers and decreases miR-221/222 levels in patients with CAD, possibly contributing to the beneficial effects of LLT with atorvastatin in this disorder.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin
  • Coronary Artery Disease / drug therapy*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Female
  • Heptanoic Acids / therapeutic use
  • Humans
  • Male
  • MicroRNAs / drug effects*
  • MicroRNAs / metabolism
  • Middle Aged
  • Pravastatin / therapeutic use
  • Prospective Studies
  • Pyrroles / therapeutic use
  • Reverse Transcriptase Polymerase Chain Reaction
  • Single-Blind Method
  • Statistics as Topic
  • Stem Cells / drug effects*
  • Stem Cells / metabolism


  • Anticholesteremic Agents
  • Heptanoic Acids
  • MicroRNAs
  • Pyrroles
  • Atorvastatin
  • Pravastatin