G-CSF after myocardial infarction accelerates angiogenesis and reduces fibrosis in swine.
OBJECTIVE
Recent studies have suggested that granulocyte colony-stimulating factor (G-CSF) may improve cardiac function after acute myocardial infarction (AMI) by accelerating angiogenesis or cardiomyogenesis, but negative results and side effect of G-CSF have also been reported. However, no previous studies have used large animal models of ischemia/reperfusion to investigate the effect and side effect of G-CSF after AMI.


METHODS
The diagonal branch of the left anterior descending coronary artery of swine was balloon-occluded for 1 h and then reperfused. The animals of the G-CSF group were injected with G-CSF subcutaneously (5.0 microg/kg/day) for 6 days after MI and then sacrificed after 4 weeks. The control group received the same volume of saline.


RESULTS
There were no differences between the groups in the rate of thrombotic obstruction or progression of stenosis lesion in coronary angiography. The ejection fraction and end-diastolic volume in the G-CSF group were not significantly improved over the control values. The fibrotic area was significantly smaller in the G-CSF group than in the controls (P<0.05), and the numbers of vessels counted in anti-von Willebrand factor and anti-alpha-smooth muscle actin-stained sections were significantly larger (P<0.005 and P<0.05, respectively). The expression of collagen III mRNA was significantly lower in the G-CSF group than in the control in the infarct (P<0.0005) and border areas (P<0.005), and TGF-beta mRNA was significantly lower in the G-CSF group in the border area (P<0.05).


CONCLUSIONS
G-CSF could modify the healing process after AMI by accelerating angiogenesis in a swine ischemia/reperfusion model. At the dose administered, however, G-CSF did not seem to improve the global cardiac function.
Sato
Takatoshi
T
Third Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Suzuki
Hiroshi
H
Kusuyama
Taro
T
Omori
Yasutoshi
Y
Soda
Teruko
T
Tsunoda
Fumiyoshi
F
Shoji
Makoto
M
Iso
Yoshitaka
Y
Koba
Shinji
S
Geshi
Eiichi
E
Katagiri
Takashi
T
Kawachi
Keisuke
K
Wakabayashi
Kohei
K
Takeyama
Youichi
Y
D000818:Animals; D021721:Balloon Occlusion; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D005355:Fibrosis / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015425:Myocardial Reperfusion / Q000379:methods; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
D015415:Biomarkers; D016179:Granulocyte Colony-Stimulating Factor