title: Pleiotropic role for monocyte C-fms protein in response to vascular injury: potential therapeutic target.
abstract: OBJECTIVE
  We examined the role of C-fms+ cells in response to vascular injury with a focus on the temporal and spatial platelet interactions, monocyte survival and proliferation within the evolving neointimal lesion and monocyte proliferation within the circulation and specified monocyte reservoir sites. Finally, we investigated the therapeutic effect of C-fms kinase inhibition (CFKI) on neointimal hyperplasia post vessel injury.
  
  
  RESULTS
  We utilized murine carotid-wire injury, a transgenic C-fms reporting mouse model, confocal microscopy, shear-flow studies, specific C-fms signalling inhibition to determine the activation, mobilization and recruitment of C-fms+ monocytes in the context of early and late vessel remodelling. C-fms+ cells were recruited as early as 4h and accumulated over time in the neointima following injury. Monocyte interaction with platelet thrombus under flow and in vivo, in addition to monocyte mobilisation into the circulation post-injury was impaired by CFKI administration. Sustained inhibition of C-fms over 1-2 weeks abrogated the neointimal response but preserved re-endothelialisation post-injury.
  
  
  CONCLUSIONS
  These data establish C-fms as a key regulator of the vascular response to injury and a potentially attractive therapeutic target in disease states where neointimal hyperplasia, monocyte activation and pathologic remodelling are prominent and endothelial homeostasis is desirable.
authors.affiliation: Centre for Research in Vascular Biology, BioSciences Institute, University College Cork, Cork, Ireland.
authors.forename: Pat
authors.initials: P
authors.lastname: Metharom
authors.forename: Kenneth
authors.initials: K
authors.lastname: Martin
authors.forename: Arun H S
authors.initials: AH
authors.lastname: Kumar
authors.forename: Neha
authors.initials: N
authors.lastname: Sawhney
authors.forename: Michael F
authors.initials: MF
authors.lastname: Cronin
authors.forename: Daniel G
authors.initials: DG
authors.lastname: McCarthy
authors.forename: Anita R
authors.initials: AR
authors.lastname: Maguire
authors.forename: Noel M
authors.initials: NM
authors.lastname: Caplice
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018056:Hemorheology; D006965:Hyperplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010973:Platelet Adhesiveness; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D057772:Vascular System Injuries / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D039481:CD11b Antigen; D047428:Protein Kinase Inhibitors; D016186:Receptor, Macrophage Colony-Stimulating Factor