Appropriate doses of granulocyte-colony stimulating factor reduced atherosclerotic plaque formation and increased plaque stability in cholesterol-fed rabbits.
OBJECTIVE
To evaluate the dose-response effects of granulocyte-colony stimulating factor (G-CSF) on atherosclerosis, we examined how G-CSF treatment at different concentrations affects atherosclerotic plaque formation in the aorta of cholesterol-fed rabbits.


METHODS
Japanese White rabbits (n=8 each) fed on a 1.5% cholesterol diet were subcutaneously injected with G-CSF at 50 (GL), 100 (GM), or 300 microg/kg/day (GH) for five days, or with 3 cycles of G-CSF at 100 microg/kg/day at 3-week intervals (GM3), or human serum albumin (Control). The extent and composition of atherosclerosis was evaluated 14 weeks after cholesterol feeding.


RESULTS
Although G-CSF treatment did not affect plasma lipid levels, the percentage of aortic surface involvement in the GM3 group was significantly decreased (p<0.05) compared with the Control group. Histological analysis revealed that the intima media ratio was also diminished in GM and GM3 groups. The extent of intimal smooth muscle cell accumulation was higher in GL and GM3 groups than in the Control group. TIMP-2 mRNA expression in the aortic tissue was increased by G-CSF treatment.


CONCLUSIONS
Our results suggest that appropriate doses of G-CSF reduced atherosclerotic plaque formation and increased plaque stability in cholesterol-fed rabbits.
Matsumoto
Taro
T
Divsion of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Watanabe
Hideyuki
H
Ueno
Takahiro
T
Tsunemi
Akiko
A
Hatano
Ben
B
Kusumi
Yoshiaki
Y
Mitsumata
Masako
M
Fukuda
Noboru
N
Matsumoto
Koichi
K
Saito
Satoshi
S
Mugishima
Hideo
H
D000818:Animals; D001018:Aortic Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008055:Lipids / Q000097:blood; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D002791:Cholesterol, Dietary; D016207:Cytokines; D008055:Lipids; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D016179:Granulocyte Colony-Stimulating Factor