Peer-Reviewed Journal Details
Mandatory Fields
Metharom, P,Martin, K,Kumar, AHS,Sawhney, N,Cronin, MF,McCarthy, DG,Maguire, AR,Caplice, NM;
2011
January
Atherosclerosis
Pleiotropic role for monocyte C-fms protein in response to vascular injury: Potential therapeutic target
Validated
()
Optional Fields
Monocytes C-fms Vascular injury C-fms kinase inhibitor Carotid wire-injury Neointimal hyperplasia COLONY-STIMULATING FACTOR MONONUCLEAR PHAGOCYTE SYSTEM CORONARY ANGIOPLASTY APOLIPOPROTEIN-E DEFICIENT MICE RESTENOSIS EXPRESSION RECEPTOR MOUSE GENE
216
74
82
Objectives: 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.Methods and 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 4 h 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.Conclusion: 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
DOI 10.1016/j.atherosclerosis.2011.01.037
Grant Details