Granulocyte Colony-Stimulating Factor Mobilizes Functional Endothelial Progenitor Cells in Patients With Coronary Artery Disease

Abstract

Objective— Endothelial progenitor cells (EPCs) that may repair vascular injury are reduced in patients with coronary artery disease (CAD). We reasoned that EPC number and function may be increased by granulocyte colony-stimulating factor (G-CSF) used to mobilize hematopoietic progenitor cells in healthy donors. Methods and Results— Sixteen CAD patients had reduced CD34 + /CD133 + (0.0224±0.0063% versus 0.121±0.038% mononuclear cells [MNCs], P <0.01) and CD133 + /VEGFR-2 + cells, consistent with EPC phenotype (0.00033±0.00015% versus 0.0017±0.0006% MNCs, P <0.01), compared with 7 healthy controls. Patients also had fewer clusters of cells in culture, with out-growth consistent with mature endothelial phenotype (2±1/well) compared with 16 healthy subjects at high risk (13±4/well, P <0.05) or 14 at low risk (22±3/well, P <0.001) for CAD. G-CSF 10 μg/kg per day for 5 days increased CD34 + /CD133 + cells from 0.5±0.2/μL to 59.5±10.6/μL and CD133 + / VEGFR-2 + cells from 0.007±0.004/μL to 1.9±0.6/μL (both P <0.001). Also increased were CD133 + cells that coexpressed the homing receptor CXCR4 (30.4±8.3/μL, P <0.05). Endothelial cell-forming clusters in 10 patients increased to 27±9/well after treatment ( P <0.05), with a decline to 9±4/well at 2 weeks ( P =0.06). Conclusions— Despite reduced EPCs compared with healthy controls, patients with CAD respond to G-CSF with increases in EPC number and homing receptor expression in the circulation and endothelial out-growth in culture.