ABSTRACT
Objective To investigate the different influences of simvastatin on proliferation of rat smooth muscle progenitor cells(SPCs) versus endothelial progenitor cells (EPCs) and identify the compounds that differentially inhibit SPCs and EPCs proliferation for clinical usefulness. Methods Total mononuclear cells (MNCs) were isolated from bone marrow of rats by Fieoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. SPCs outgrew from the culture of MNCs in the presence of platelet-derived growth factor-BB and basic fibroblast growth factor, whereas EPCs were obtained in the presence of vascular endothelial growth factor. SPCs were identified as adherent cells positive for α-smooth muscle actin (α-SMA) by indirect immunofluoreseent staining. EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining. SPCs and EPCs were stimulated by simvastatin (0.01～10.00 μmol/L) or vehicle control for the respective time points (6 h, 12 h, 24 h and 48 h). SPCs and EPCs proliferation were assayed with 3H-TdR incorporation and manual counting respectively. Results Simvastatin obviously inhibited SPCs proliferation. At the concentration of 0. 01 μmol/L for 12 h,simvastatin significantly reduced the number of SPCs by (5.8±3.1)% compared with control group (P<0.05). Simvastatin significantly stimulated EPCs proliferation, which was dose- and time dependent and reached maximum at 1 μmol/L after 24 hours (2.0±0.1 fold increase, P<0.01).Conclusions Simvastatin displays different effects on SPCs (inhibited) and EPCs (promoted)proliferation. Local application of simvastatin may inhibit arterial restenosis and promote reendothelialization of injured vessels.
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Objective To evaluate the clinical outcome of stent placement in the superior vena cava (SVC) syndrome. Methods Twelve patients with stenosis of the superior vena cava and/or its main tributaries underwent placement of a self-expanding endovascular Wallstents (11 men,1 woman,mean age 51 years). Results Until death or completion of the study,the SVC syndrome was successfully controlled in 92% of the cases (11/12). There were no early procedure-related complications such as early occlusion,or migration of the stent. The recurrence rate was 16.7%. Conclusion Percutaneous venous stent placement in the superior vena cava is a relatively safe and simple procedure. In majority of cases,the symptoms of the SVC syndrome are relieved immediately and completely. Complications are rare.
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AIM: To evaluate the mobilization of endothelial progenitor cells (EPCs) in mice peripheral blood during hindlimb ischemia alone or in combination with granulocyte colony stimulating factor (G-CSF). METHODS: Hindlimb ischemia was established in mice by surgical excision of both femoral arteries. Fluorescence-activated cell sorting (FACS) was used to detect the expression of cell-surface CD34 and vascular endothelial growth factor recepter-2 (VEGFR2) antigens. The ratio of double-positive cells for CD34 and VEGFR2 was regarded as the level of EPCs in peripheral blood. In G-CSF administration in combination with hindlimb ischemia group, the percentage of double-positive cells was also detected. RESULTS: As compared with control group, hindlimb ischemia increased the percentage of EPCs in mice peripheral blood. The hindlimb ischemia combined with G-CSF administration significantly enhanced the percentage of EPCs. CONCLUSION: Ischemia increases the number of EPC in peripheral blood. It may induce the migration of EPC from barrow to peripheral blood. By mobilizing barrow, G-CSF enhances this effect.
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Objective To study the effect of endothelial progenitor cells mobilization on vascular endothelial repair after carotid artery injury in rats.Methods The rat balloon-injured carotid model was established.In the control group:saline was administrated intragastrically;the simvastatin group:simvastatin 10 mg/(kg?d)was administrated intragastrically and in the simvastatin+ granulocyte colony stimulating factor(G-CSF)group:G-CSF 100 ?g/(kg?d)was intraperitoneally injected togother with intragastrical simvastatin from 1 week before operation to 2 weeks after operation.The repair rate of injuried endothelium,neointima/media area ratio(IA/MA),the positive cell index of proliferating cell nuclear antigen(PCNA)and nitric oxide(NO)release in peripheral blood were detected.In addition,the ratio of CD34+VEGFR2+ double positive expression cell was detected by fluorescence activated cell sorter(FACS),which indicated the level of EPCs.Results The repair rate of injured endothelium was increased(12.3%)in the simvastatin group compared with the control group;IA/MA was reduced 18.4%;NO release was increased 33.9% and the positive cell index of PCNA was reduced 5.7%.These data were 38.2%,50.3%,33.9% and 37.2% respectively in simvastatin+G-CSF group.Compared with the control group,the ratio of CD34+VEGFR2+ double positive expression cell was increased 87.6% in peripheral blood,and it increasd 343.4% in simvastatin+G-CSF group.Conclusion The results suggest the possibility that simvastatin may promote the EPCs from bone marrow to peripheral blood,so it can improve the effect of repair rate of injured endothelium and inhibit neointimal hyperplasia.In addition,G-CSF can enhance the effect of simvastatin on the injured endothelium and neointima hyperplasia.
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AIM: To investigate the feasibility of transplanting endothelial progenitor cells(EPCs) obtained from spleen in vascular endothelium repairmen after vascular injury.METHODS: EPCs were isolated by using a Ficoll density gradient centrifugation,and were cultured in plate.The endothelial characteristics of EPCs were identified by immunochemical staining and fluorescent labeling.Dil-Ac-LDL labeled spleen-derived EPCs were transplanted into the rats by intravenous injection directly after induction of arterial injury and again 24 hours later.Rats received FITC-labeled lectin intravenously before euthanasia.The distribution of fluorescent labeled EPCs was traced.The morphology of arterial intima and media was studied by optical microscopy and image analysing system.RESULTS: The adherent cells were considered EPCs that showed spindle shape and form blood-siland-like structures during development.The adherent cells had many endothelial characteristics.Fluorescent labeling showed that the intravenously injected EPCs specifically restricted to the vascular injury site,and lectin binding confirmed the endothelial phenotype.The ratio of neointimal/media area in EPCs transplantation group was obviously reduced than that in injury group and M199 group(0.82?0.09 vs 1.52?0.21,1.48?0.19,P