Abstract
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 microg/(kg x 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzylamines
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Bone Marrow Cells / cytology
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / physiology
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Cell Differentiation / drug effects*
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Cell Differentiation / physiology
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Cell Proliferation / drug effects
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Chemokine CCL2 / genetics
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Chemokine CCL2 / physiology
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Chemokine CXCL12
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Chemokines, CXC / genetics
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Chemokines, CXC / physiology*
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Cyclams
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / physiology
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Gene Expression Regulation / drug effects
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Heterocyclic Compounds / pharmacology
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Interleukin-10 / genetics
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Interleukin-10 / physiology
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Interleukin-6 / genetics
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Interleukin-6 / physiology
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Macrophage Colony-Stimulating Factor / pharmacology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Receptors, CXCR4 / antagonists & inhibitors
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Receptors, CXCR4 / drug effects
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Receptors, CXCR4 / genetics
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Receptors, CXCR4 / physiology*
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Signal Transduction / physiology
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Stem Cells / cytology
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Stem Cells / drug effects*
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Stem Cells / physiology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / physiology
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Tunica Intima / cytology
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Tunica Intima / drug effects
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Tunica Intima / physiology
Substances
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Benzylamines
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CXCL12 protein, human
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CXCR4 protein, mouse
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Ccl2 protein, mouse
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Chemokine CCL2
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Chemokine CXCL12
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Chemokines, CXC
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Cxcl12 protein, mouse
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Cyclams
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Heterocyclic Compounds
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Interleukin-6
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Receptors, CXCR4
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Macrophage Colony-Stimulating Factor
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