title: M-CSF accelerates neointimal formation in the early phase after vascular injury in mice: the critical role of the SDF-1-CXCR4 system.
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.
  
  
  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.
authors.affiliation: Division of Cardiovascular Sciences, Department of Organ Regeneration, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shiba
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yajima
authors.forename: Hajime
authors.initials: H
authors.lastname: Morimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Izawa
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Ise
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Kazuo
authors.initials: K
authors.lastname: Motoyoshi
authors.forename: Uichi
authors.initials: U
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D001596:Benzylamines; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology*; D000080027:Cyclams; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects / Q000502:physiology
chemical_list: D001596:Benzylamines; C515255:CXCL12 protein, human; C514936:CXCR4 protein, mouse; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D015850:Interleukin-6; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor; C088327:plerixafor