G-CSF administration after myocardial infarction in mice attenuates late ischemic cardiomyopathy by enhanced arteriogenesis.
Granulocyte-colony stimulating factor (G-CSF) has been shown to improve cardiac function after myocardial infarction (MI) by bone marrow cell mobilization and by protecting cardiomyocytes from apoptotic cell death. However, its role in collateral artery growth (arteriogenesis) has not been elucidated. Here, we investigated the effect of G-CSF on arteriolar growth and cardiac function in a murine MI model. Mice were treated with G-CSF (100 microg/kg/day) directly after MI for 5 consecutive days. G-CSF application resulted in a significant increase of circulating mononuclear cells expressing stem cell markers. Arterioles in the border zone of infarcted myocardium showed an increased expression of ICAM-1 accompanied by an accumulation of bone marrow derived cells and a pronounced proliferation of endothelial and smooth muscle cells. Histology of G-CSF treated mice revealed a lower amount of granulation tissue (67.8 vs. 84.4%) associated with a subsequent reduction in free LV wall thinning and scar extension (23.1 vs. 30.8% of LV). Furthermore, G-CSF treated animals showed a significant improvement of post-MI survival (68.8 vs. 46.2%). Pressure-volume relations revealed a partially restored myocardial function at day 30 (EF: 32.5 vs. 17.2%). Our results demonstrate that G-CSF administration after MI stimulates arteriogenesis and attenuates ischemic cardiomyopathy after MI.
Ludwig-Maximilians University, Klinikum Grosshadern, Medical Department I, Marchioninistr. 15, D-81377 Munich, Germany.
Elisabeth
E
Deindl
Marc-Michael
MM
Zaruba
Stefan
S
Brunner
Bruno
B
Huber
Ursula
U
Mehl
Gerald
G
Assmann
Imo E
IE
Hoefer
Josef
J
Mueller-Hoecker
Wolfgang-Michael
WM
Franz
D000818:Animals; D003331:Coronary Vessels / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016176:T-Lymphocyte Subsets
D016179:Granulocyte Colony-Stimulating Factor