Published online before print November 29, 2004, doi: 10.1161/01.ATV.0000151690.43777.e4
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© 2005 American Heart Association, Inc.
Vascular Biology |
Granulocyte Colony-Stimulating Factor Mobilizes Functional Endothelial Progenitor Cells in Patients With Coronary Artery Disease
From the Cardiovascular Branch, National Heart, Lung, and Blood Institute and the Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Md.
Correspondence to Richard O. Cannon III, MD, National Institutes of Health, Building 10 Room 7B15, 10 Center Drive MSC 1650, Bethesda, MD 20892-1650. E-mail cannonr{at}nih.gov
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.
Endothelial progenitor cells (EPCs) are reduced in coronary artery disease. Granulocyte colony-stimulating factor (CSF) administered to patients increased: (1) CD133+/VEGFR-2+ cells consistent with EPC phenotype; (2) CD133+ cells coexpressing the chemokine receptor CXCR4, important for homing of EPCs to ischemic tissue; and (3) endothelial cell-forming clusters in culture. Whether EPCs mobilized into the circulation will be useful for the purpose of initiating vascular growth and myocyte repair in coronary artery disease patients must be tested in clinical trials.
Key Words: coronary disease • atherosclerosis • angiogenesis • cell adhesion molecules • cells
Related Article:
Arterioscler. Thromb. Vasc. Biol. 2005 25: 270-271.
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