M-CSF accelerates neointimal formation in the early phase after vascular injury in mice the critical role of the SDF-1-CXCR4 system
M-CSF accelerates neointimal formation in the early phase after vascular injury in mice the critical role of the SDF-1-CXCR4 system
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DOI：
10.1161/01.atv.0000250606.70669.14
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发表时间：
2007-02-01
影响因子：
8.7
通讯作者：
Ikeda, Uichi
中科院分区：
文献类型：
--
作者：
Shiba, Yuji;Takahashi, Masafumi;Ikeda, Uichi
由于巨噬细胞集落刺激因子（M-CSF）已被证明刺激单核细胞/巨噬细胞谱系的分化和增殖，并参与血管损伤后新生内膜形成的过程，我们测试了M-CSF对小鼠血管损伤后新生内膜形成中骨髓来源的祖细胞募集的影响。介导的血管损伤在C57 BL/6小鼠的股动脉中产生。从损伤前4天开始，连续10天给予重组人M-CSF [ 500 μ g/（kg.day）]或盐水（对照）。用M-CSF处理加速损伤后早期的新生内膜形成，并且这种新生内膜病变主要由骨髓源性细胞组成。M-CSF治疗对内皮祖细胞（EPCs：CD 34（+）/Flk-1（+））的动员和损伤后的再内皮化没有影响。基质细胞衍生因子-1（SDF-1）在损伤后的新生内膜和中膜中有明显表达，而CXCR 4（+）细胞在新生内膜中观察到。此外，一种新的CXCR 4拮抗剂，AMD 3100，显着衰减的M-CSF诱导的neointimal formation. Conclusions，这些研究结果表明，M-CSF加速血管损伤后的新生内膜形成通过SDF-1-CXCR 4系统，抑制该系统具有治疗心血管疾病的治疗潜力。
Objective-Since the macrophage colony-stimulating factor ( M-CSF) has been shown to stimulate differentiation and proliferation of monocyte/macrophage lineage and to be involved in the process of neointimal formation after vascular injury, we tested the effects of M-CSF on the recruitment of bone marrow-derived progenitor cells in neointimal formation after vascular injury in mice.Methods and Results-Wire-mediated vascular injury was produced in the femoral artery of C57BL/6 mice. Recombinant human M-CSF [ 500 mu g/( kg.day)] or saline ( control) was administered for 10 consecutive days, starting 4 days before the injury. Treatment with M-CSF accelerated neointimal formation in the early phase after injury, and this neointimal lesion mainly consisted of bone marrow - derived cells. M-CSF treatment had no effect on the mobilization of endothelial progenitor cells ( EPCs: CD34(+)/Flk-1(+)) and reendothelialization after injury. The stromal cell-derived factor-1 ( SDF-1) was markedly expressed in the neointima and media after injury, whereas CXCR4(+) cells were observed in the neointima. Further, a novel CXCR4 antagonist, AMD3100, significantly attenuated the M-CSF - induced neointimal formation.Conclusions-These findings suggest that M-CSF accelerated neointimal formation after vascular injury via the SDF-1-CXCR4 system, and the inhibition of this system has therapeutic potential for the treatment of cardiovascular diseases.