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

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.