G-CSF Mobilizes Endothelial Progenitor Cells in Coronary

循环内皮祖细胞(EPC)可能具有修复心血管损伤的功能，但在冠心病(CAD)患者中则减少。16例冠心病患者外周血中CD34+/CD133+(0.0224±0.0063比0.121±0.038%)和CD133+/VEGFR-2+符合内皮祖细胞表型的细胞(0.00033±0.00015比0.0017±0.0006%，P&lt；0.01)。与16名高危健康受试者(每孔13？4个)或14名低危受试者(22？3个/孔，P&lt；0.001)相比，在培养1周时，与成熟内皮细胞表型一致的细胞簇数(2？1个/孔)明显少于16例健康受试者(13？4个/孔，P&lt；0.05)。G-CSF10ig/kg/d，连续5d，可使外周血中CD34+/CD133+细胞由0.50.2升至59.510.6/il，CD133+/VEGFR-2+细胞由0.007 0.004升至1.90.6/il(P均<0.001)。G-CSF还增加了共表达趋化因子受体CXCR4的CD133+细胞(30.4±8.3/il，P&lt；0.05)，这可能是EPC归巢到缺血组织的重要因素。10例患者治疗后内皮细胞形成簇增加到27？9个/孔(P&lt；0.05)，治疗后2周下降到9？4个/孔(P=0.06)。 结论：与健康对照组相比，尽管循环中造血系的EPC数量和培养中的内皮细胞集落数量减少，但CAD患者对G-CSF的反应是循环中的EPC数量和培养的内皮细胞扩增能力增加。动员到循环中的内皮祖细胞是否有助于启动冠心病患者的血管生长和心肌细胞修复，必须在临床试验中进行测试

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