Cilostazol Enhances Mobilization of Circulating Endothelial Progenitor Cells and Improves Endothelium-Dependent Function in Patients at High Risk of Cardiovascular Disease

Angiology. 2016 Aug;67(7):638-46. doi: 10.1177/0003319715606249.

Abstract

This is the first study to investigate the vasculoangiogenic effects of cilostazol on endothelial progenitor cells (EPCs) and flow-mediated dilatation (FMD) in patients at high risk of cardiovascular disease (CVD). This double-blind, placebo-controlled study included 71 patients (37 received 200 mg/d cilostazol and 34 received placebo for 12 weeks). Use of cilostazol, but not placebo, significantly increased circulating EPC (kinase insert domain receptor(+)CD34(+)) counts (percentage changes: 149.0% [67.9%-497.8%] vs 71.9% [-31.8% to 236.5%], P = .024) and improved triglyceride and high-density lipoprotein cholesterol levels (P = .002 and P = .003, respectively). Plasma levels of vascular endothelial growth factor (VEGF)-A165 and FMD significantly increased (72.5% [32.9%-120.4%] vs -5.8% [-46.0% to 57.6%], P = .001; 232.8% ± 83.1% vs -46.9% ± 21.5%, P = .003, respectively) in cilostazol-treated patients. Changes in the plasma triglyceride levels significantly inversely correlated with the changes in the VEGF-A165 levels and FMD. Cilostazol significantly enhanced the mobilization of EPCs and improved endothelium-dependent function by modifying some metabolic and angiogenic markers in patients at high risk of CVD.

Keywords: cardiovascular disease; cilostazol; endothelial function; endothelial progenitor cells; flow-mediated dilatation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antigens, CD34 / blood
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / drug therapy*
  • Cell Movement / drug effects
  • Cilostazol
  • Double-Blind Method
  • Endothelial Progenitor Cells / drug effects*
  • Endothelium, Vascular / drug effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neovascularization, Physiologic / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use
  • Risk Factors
  • Statistics as Topic
  • Tetrazoles / pharmacology*
  • Tetrazoles / therapeutic use*
  • Triglycerides / blood
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-2 / blood

Substances

  • Antigens, CD34
  • Platelet Aggregation Inhibitors
  • Tetrazoles
  • Triglycerides
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Cilostazol