G-CSF Mobilizes Endothelial Progenitor Cells in Coronary

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Circulating endothelial progenitor cells (EPCs) may function to repair cardiovascular injury, but are reduced in patients with coronary artery disease (CAD). Granulocyte colony-stimulating factor (G-CSF) mobilizes CD34+ hematopoietic progenitor cells, but whether this cytokine mobilizes EPCs of this lineage in CAD patients is unknown.Sixteen CAD patients had reduced circulating 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 for 1 week with out-growth consistent with mature endothelial phenotype (2?1 per well) compared with 16 healthy subjects at high risk (13?4 per well, P<0.05) or 14 subjects at low risk (22?3 per well, P<0.001) for CAD. G-CSF 10 ig/kg/day for 5 days increased CD34+/CD133+ cells in blood from 0.5?0.2 to 59.5?10.6/iL and CD133+/ VEGFR-2+ cells from 0.007?0.004 to 1.9?0.6/iL (both P<0.001). Also increased by G-CSF were CD133+ cells that coexpressed the chemokine receptor CXCR4 (30.4?8.3/iL, P<0.05) that may be important for homing of EPCs to ischemic tissue. Endothelial cell-forming clusters in 10 patients increased to 27?9 per well post-treatment (P<0.05), with a decline to 9?4 per well at 2 weeks (P=0.06). Conclusions- Despite reduced numbers of EPCs of hematopoietic lineage in the circulation and endothelial cell-forming clusters in culture compared with healthy controls, CAD patients respond to G-CSF with increases in EPC number in the circulation and endothelial out-growth capacity in culture. Whether EPCs mobilized into the circulation will be useful for the purpose of initiating vascular growth and myocyte repair in CAD patients must be tested in clinical trials