G-CSF Mobilizes Endothelial Progenitor Cells in Coronary

循环内皮祖细胞（EPCs）可能具有修复心血管损伤的功能，但在冠状动脉疾病（CAD）患者中功能降低。粒细胞集落刺激因子（G-CSF）可动员CD34+造血祖细胞，但这种细胞因子是否能动员CAD患者的这一谱系的EPCs尚不清楚。16例CAD患者循环CD34+/CD133+ （0.0224 ~ 0.0063 vs 0.121 ~ 0.038%单核细胞[MNCs]， P<0.01）和CD133+/VEGFR-2+细胞（0.00033 ~ 0.00015 vs 0.0017 ~ 0.0006% MNCs， P<0.01）与7例健康对照相比减少。患者在培养1周后也有较少的细胞簇，其生长与成熟的内皮表型一致(2？每孔1例)，而16名健康高风险受试者(13？每孔4例，P<0.05)或低风险14例(22？3口井，P<0.001)。G-CSF 10 ig/kg/d使血中CD34+/CD133+细胞从0.5 ~ 0.2 /iL增加到59.5 ~ 10.6/iL， CD133+/ VEGFR-2+细胞从0.007 ~ 0.004增加到1.9 ~ 0.6/iL （P均<0.001）。G-CSF也增加了共表达趋化因子受体CXCR4的CD133+细胞（30.4 ~ 8.3/iL， P<0.05），这可能对EPCs向缺血组织的归巢很重要。内皮细胞形成簇从10例增加到27例。处理后每口井9个（P<0.05），降至9个？2周时每口井4颗（P=0.06）。

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