Cilostazol Improves Proangiogenesis Functions in Human Early Endothelial Progenitor Cells through the Stromal Cell-Derived Factor System and Hybrid Therapy Provides a Synergistic Effect In Vivo

Figure 2

Stimulating effects of cilostazol on the expression of endothelial lineage markers and angiogenesis functions in human early EPCs. (a) Representative images of the expression of VEGF-R2 (green) and CD31 (red) by immunofluorescence staining. PBS treatment was performed as a vehicle control. A CXCR4 inhibitor, AMD3100, was used to suppress the effect of cilostazol with highest dose (30 μM). The length of the bar is 100 μm. (b) Quantification results for the expression of VEGF-R2 or CD31 after treatment with different doses of cilostazol. The stimulating effect of cilostazol could be attenuated with AMD3100. Results were shown in ratio of VEGF-R2⁺ (CD31⁺)/DAPI⁺. (c) SDF-1α was used as a positive control. Cilostazol enhanced colony formation (c), proliferation (d), migration (e), and antiapoptosis (f) in human early EPCs. These effects were reversed by inhibitors. , , and , significantly different compared with vehicle control. and , significantly different compared with cilostazol-treated (30 μM) cells alone. BrdU, 5-bromo-2′-deoxyuridine; CFU, colony-forming unit; DAPI, 4′,6-diamidino-2-phenylindole; PBMCs, peripheral blood mononuclear cells; SDF-1α, stromal cell-derived factor-1α; VEGF-R2, vascular endothelial growth factor receptor type 2.

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