| Vascular endothelial cell dysfunction is associated with atherosclerosis. The vascular endothelium denudation and endothelial dysfunction have been shown in procedure of percutaneous coronary intervention(PCI). The damage of vascular endothelial cells(ECs) and the proliferation and migration of vascular smooth muscle cells(SMCs) are the major causes of neointima formation, endothelium denudation also play a crucial role in in-stent resterosis after PCI. More and more researches have been done to prevent resterosis , previous investigations discovered that brachytherapy and drug-eluting stent on reduced in-stent resterosis by inhibiting SMCs overgrowth. The sirolimus eluting stent was used in clinical practices. However, whether brachytherapy or cytostatic inhibitor, its effect on cell proliferation is non-specific, and may be take some worry about long-term safety, such as insufficient endothelium repair, stent exposition, late stent thrombosis and so on. If the processes of endothelium repair can be improved as well as inhibiting SMCs overgrowth, it may lead to reducing the rate of in-stent restenosis, ameliorating vessel remodeling and accelerating recovery of the damaged vascular function. Reendotheliazation has classically been thought to recruit from the migration and proliferation of endothelial cells from viable endothelium adjacent to the site of injury. With the researches be studied more intensively, it discovered that bone marrow-derived stem cells were capable of incorporating the processes of endothelium repair as well as participating neoangiogenesis and neovascularization. It has been found the presence of bone marrow-derived endothelial precursor cells in peripheral blood, also be called endothelial progenitor cells(EPCs), not only amplificated itself, but also differentiated into mature ECs. At present, the methods identifying EPC in peripheral blood include cell culture, immuno-magetic bead selection and fluorescence activated cell sorter(FACS) . When FACS be used, the variable EPC level can be reflected by the proportion of This work was funded by Natioal Natural Science Foundation of China (NO:30270568)CD34+AC133+ or CD34+VEGFR2+ double positive expression cell. The EPC number in peripheral blood was few in normal physiological conditions, it increased when affected by ischemia , vessel injury or other factors, indicated that it may be associated with promoted process of vascular endothelium repair. Measures accelerated EPC releasing from bone marrow into peripheral blood were called bone marrow mobilization. Some studies have discovered that infused exogenous bone marrow-derived stem cells into injured vessel models were involved in reendothelialization of the vascular lesions. It has not been clarified whether any factors such as drugs or cytokines could increase the circulating EPCs number, and then accelerate reendothelialization of injured vessels by autogenous bone marrow mobilization. Related investigations are lacking. If the target roles and modulate mechanisms are revealed further, the more supporting investigations will be offered for promoting the process of endothelium repair and preventing restenosis. Statins possess favorable effects on the primary and secondary prevention of coronary heart disease, it also exhibited the positive effect on ECs function which is independent of low-density lipoprotein cholesterol(LDL-C) reduction. Granulocyte Colony-stimulating factor(G-CSF) displayed mobilizing peripheral blood progenitor cells. But the relationship between the circulating EPCs and statins or G-CSF is not clear. In this experiment, simvastatin will be administrated alone or in combination with G-CSF in hindlimb ischemic mice in order to increase the number of circulating EPCs, then the similar administration will be given at the rat carotid balloon-injury model, the effect on endothelium repair and neointima formation will be observed. Methods:1. The proportion of circulating EPCs in hindlimb ischemic mice was evaluated: simvastatin alone or in combination with G-... |
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