The effects of granulocyte-colony stimulating factor in bare stent and sirolimus-eluting stent in pigs following myocardial infarction.
OBJECTIVE
The purpose of this study was to compare the effects of granulocyte-colony stimulating factor (G-CSF) on in-stent restenosis (ISR) in bare and sirolimus-eluting stents (SES) in a porcine myocardial infarction model.


BACKGROUND
Using G-CSF to mobilize stem cells has shown promise in infarcted heart. However, G-CSF may aggravate ISR and an aggressive strategy to prevent ISR is needed.


METHODS
Bare stents and SES were implanted in coronary arteries (Group I, bare stents; Group II, bare stents with G-CSF; Group III, SES; Group IV, SES with G-CSF, n=10 in each group) 72 h after experimental myocardial infarction (MI). G-CSF (10 microg/kg/day) was injected for 7 days from 24 h after stent implantation.


RESULTS
In coronary angiographic and histomorphometric analysis, percent area stenosis was significantly increased in Group II compared with that in Group I at 28 days (P<0.05). The ratio of inflammatory cells in the neointima was higher in Group II (P<0.05). No significant differences were observed between Group III and IV. In Group II, phosphorylated signal transducers and activators of transcription (STAT)-3, STAT-3, and vascular endothelial growth factor (VEGF) showed increased neointimal expression. In porcine aortic smooth muscle cells (PASMC), G-CSF increased the growth rate, migration, STAT-3 phosphorylation, and VEGF, which were suppressed by rapamycin and AG490, a STAT-3 inhibitor.


CONCLUSIONS
STAT-3 and VEGF are important in the development of enhanced ISR by G-CSF in bare stents. SES could be a good strategy to prevent the G-CSF-stimulated proliferation and migration of smooth muscle cells, which could be responsible for neointimal hyperplasia.
Lim
Sang Yup
SY
The Heart Center of Chonnam National University Hospital, Gwangju, South Korea.
Kim
Yong Sook
YS
Ahn
Youngkeun
Y
Jeong
Myung Ho
MH
Rok
Lee Sang
LS
Kim
Ju Han
JH
Kim
Key Hun
KH
Park
Hyung Wook
HW
Kim
Weon
W
Cho
Jeong Gwan
JG
Park
Jong Chun
JC
Kang
Peter M
PM
Schwartz
Robert S
RS
Kang
Jung Chaee
JC
D000704:Analysis of Variance; D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D001774:Blood Chemical Analysis; D049109:Cell Proliferation / Q000187:drug effects; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000628:therapy*; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000494:pharmacology*; D015607:Stents; D034421:Sus scrofa
D016179:Granulocyte Colony-Stimulating Factor; D020123:Sirolimus