OBJECTIVETo investigate the effects of granulocyte colony-stimulating factor (G-CSF) on peripheral endothelial progenitor cells (EPC) and atherosclerosis (AS) in cholesterol-fed rabbits.

METHODSMale New Zealand white rabbits were randomly divided into control group, G group (Recombinant Human Granulocyte Colony Stimulating Factor Injection rhG-CSF 50 microg/d), AS group (high cholesterol diet) and G + AS group (rhG-CSF 50 microg/d plus high cholesterol diet, n = 8 per group). Peripheral blood was collected at baseline and at 1, 4, 8 and 12 weeks, total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. After being cultured for 7 days, EPCs were characterized as adherent cells double positive for DiLDL uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope. After being cultured for 3 days, the number of EPC (PE-CD34/FITC-CD133 double-stained positive cells) was quantified by flow cytometric analysis. Serum NO was measured and aortic plaque area analyzed at 12 weeks.

RESULTSEPC number was low in control and AS groups and EPC number was significantly increased ( approximately 13-fold, P < 0.001) compared to baseline at 1 week in G and G + AS groups and remained at this level throughout the study period in G group while decreased gradually in G + AS group and returned to baseline level at 12 weeks. Aortic atherosclerotic plaque was visible in both AS and G + AS groups, however, the aortic atherosclerotic plaque area was smaller in G + AS group than that of in As group (59.8 mm(2) +/- 26.9 mm(2) vs. 251.5 mm(2) +/- 83.4 mm(2), P < 0.01). Serum NO was similar between AS and G + AS groups and significantly higher than that in control and G groups.

CONCLUSIONCSF could attenuate atherosclerosis in cholesterol-fed rabbits by increasing circulating EPC.