Granulocyte colony-stimulating factor (G-CSF) accelerates reendothelialization and reduces neointimal formation after vascular injury in mice.
OBJECTIVE
Neointimal formation following percutaneous coronary intervention (PCI), termed restenosis, limits therapeutic revascularization. Since reendothelialization is one of the determinant factors for the development of neointimal formation, we examined the effects of granulocyte colony-stimulating factor (G-CSF) on reendothelialization and neointimal formation after vascular injury in mice.


RESULTS
Wire-mediated vascular injury was produced in the femoral artery of C57BL/6 mice. G-CSF pretreatment significantly accelerated reendothelialization and decreased neointimal formation following vascular injury; however, this inhibitory effect of G-CSF was diminished when G-CSF was started following the injury. Flow cytometry analysis revealed that G-CSF treatment increased the number of endothelial progenitor cells (EPCs: CD34+/Flk-1+) in the peripheral circulation. Vascular injury was also produced in 2 types of mice whose bone marrow was replaced with that of enhanced green fluorescent protein- and Tie2/LacZ-transgenic mice. In the reendothelialized artery of these mice, few bone marrow-derived EPCs were detected. Furthermore, G-CSF treatment reduced the serum level of interleukin (IL)-6.


CONCLUSIONS
G-CSF treatment accelerated reendothelialization and decreased neointimal formation following vascular injury, although there was little contribution of bone marrow-derived EPCs to the reendothelialization of the artery. These results suggest that G-CSF pretreatment has a therapeutic potential for prevention of restenosis following PCI.
Yoshioka
Toru
T
Division of Cardiovascular Science, Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan.
Takahashi
Masafumi
M
Shiba
Yuji
Y
Suzuki
Chihiro
C
Morimoto
Hajime
H
Izawa
Atsushi
A
Ise
Hirohiko
H
Ikeda
Uichi
U
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D005263:Femoral Artery / Q000276:immunology / Q000293:injuries / Q000473:pathology; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D023421:Models, Animal; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011994:Recombinant Proteins; D013234:Stem Cells / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology; D001616:beta-Galactosidase / Q000235:genetics
D015850:Interleukin-6; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase