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.
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 humanM-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: Hana Verescakova; Gabriela Ambrozova; Lukas Kubala; Tomas Perecko; Adolf Koudelka; Ondrej Vasicek; Tanja K Rudolph; Anna Klinke; Steven R Woodcock; Bruce A Freeman; Michaela Pekarova Journal: Free Radic Biol Med Date: 2017-01-04 Impact factor: 7.376
Authors: Weiyi Feng; Maria Madajka; Bethany A Kerr; Ganapati H Mahabeleshwar; Sidney W Whiteheart; Tatiana V Byzova Journal: Blood Date: 2011-01-11 Impact factor: 22.113
Authors: Brian K Stansfield; Waylan K Bessler; Raghuveer Mali; Julie A Mund; Brandon D Downing; Reuben Kapur; David A Ingram Journal: Am J Pathol Date: 2013-11-07 Impact factor: 4.307
Authors: Karen C Young; Eneida Torres; Konstantinos E Hatzistergos; Dorothy Hehre; Cleide Suguihara; Joshua M Hare Journal: Circ Res Date: 2009-05-07 Impact factor: 17.367
Authors: Michelle Olive; Jason A Mellad; Leilani E Beltran; Mingchao Ma; Thomas Cimato; Audrey C Noguchi; Hong San; Richard Childs; Jason C Kovacic; Manfred Boehm Journal: J Clin Invest Date: 2008-06 Impact factor: 14.808