High-dose granulocyte-colony stimulating factor promotes neointimal hyperplasia in the early phase and inhibits neointimal hyperplasia in the late phase after vascular injury.
BACKGROUND
Granulocyte-colony stimulating factor (G-CSF) affects injured arteries through early endothelialization. Some reports, however, have cautioned that the restenosis rate may increase after G-CSF injection. In the present study, high-dose G-CSF was administered to mice with vascular injury to clarify its effect.


RESULTS
Mice were received daily subcutaneous injections of saline or a high dose (300 microg/kg) of G-CSF for 5 days after vascular injury. In the FACS analysis, CD34-/Sca-1-positive progenitor cells were more abundant in the G-CSF group (p<0.05). Neointimal hyperplasia was more evident in the G-CSF group at 1 week (p<0.05), whereas at 4 weeks it was more evident in the control group (p<0.01). TUNEL-positive cells in the arterial wall were more numerous in the G-CSF group at day 1 (p<0.01). CD34-positive cells were observed in the G-CSF group at 1 week. Re-endothelialization appeared earlier in the G-CSF group (at 4 weeks; p<0.01). An increased number of 1A4-positive smooth muscle cells were found in bone marrow cell culture treated with G-CSF.


CONCLUSIONS
High-dose G-CSF induced neointimal proliferation through excessive inflammation and bone marrow cell mobilization in the early phase. In the late phase, however, it induced early re-endothelialization and thereby inhibited neointimal hyperplasia.
Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Makoto
M
Shoji
Yoshitaka
Y
Iso
Taro
T
Kusuyama
Yasutoshi
Y
Omori
Teruko
T
Soda
Fumiyoshi
F
Tsunoda
Takatoshi
T
Sato
Shinji
S
Koba
Eiichi
E
Geshi
Youichi
Y
Kobayashi
Takashi
T
Katagiri
Hiroshi
H
Suzuki
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005263:Femoral Artery / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology*; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects* / Q000494:pharmacology; D006965:Hyperplasia; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology*
D018952:Antigens, CD34; D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D016179:Granulocyte Colony-Stimulating Factor