Erythropoietin Mobilizes The KDR~+ Stem Cells From Bone Marrow To Peripheral Blood Via SDF-1α And Repairs Acute Myocardial Infarction In Mice

Background Acute myocardial infarction is the terminal event of atherosclerosis. It is a major cause of death and disability. In addition to the traditional drugs, coronary stent and bypass surgery to restore blood supply to therapy myocardial infarction, the use of stem cells in promoting angiogenesis is a new method being studied. A variety of cytokines and drugs can mobilize endothelial progenitor cells from bone marrow. In addition to hematopoietic stem cells, erythropoietin can mobilize endothelial progenitor cells to play a protective role in myocardial infarction.Aim To study whether erythropoietin has effect on bone marrow KDR+ stem cells and the possible mechanism in mice with acute myocardial infarction (AMI)Methods Acute myocardial infarction mice were established by cryoinjury. Sixty male mice were randomly divided into four groups after cryoinjury:①EPO administration group: AMI+EPO ( 1000u/kg ) ,②AMD3100 inhibition group: AMI+EPO+AMD3100(EPO:1000u/kg,AMD3100:5mg/kg),③control group: AMI+PBS,④sham surgery group: PBS. EPO was administrated to EPO administration group and AMD3100 inhibition group for 4 days. Then on day 5, PBS and AMD3100 were administrated respectively. PBS was administrated to control group and sham surgery group for 5 days. The changes of KDR positive cells in peripheral blood were determined by flowcytometry. Immunohistochemistry was used to detect capillary density of peri-infarct area in 2 and 4 weeks after surgery. Results Compared with control group and sham surgery group, the number of KDR positive cells in peripheral blood increased in EPO administration group (2.88%±0.67% VS 0.68%±0.24% VS 0.62%±0.24%, P <0.05) Compared with EPO group, the number of KDR positive cells decreased in AMD3100 inhibition group (0.28%±0.13%). Two and four weeks after acute myocardial infarction modeling, the capillary density in EPO administration group was significantly higher than that in AMD3100 group and control group(P <0.05). But only 2 weeks after surgery, the capillary density in AMD3100 inhibition group was higher than that in control group(P <0.05).Conclusions EPO can effectively mobilize KDR+ stem cells from bone marrow to peripheral blood, which may increased capillary density in peri-infarct area in mice with acute myocardial infarction. The effect can be completely restrained by AMD3100, which suggested that EPO may mobilize KDR+ cells in bone marrow to peripheral blood by SDF-1α/CXCR4 axis.