Granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor exacerbate atherosclerosis in apolipoprotein E-deficient mice.
BACKGROUND
Recent studies have suggested a potential contribution of bone marrow-derived progenitor cells to vascular repair. Preliminary clinical studies have explored the possibility that mobilization of progenitor cells with granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) can affect vascular repair. However, it is not known whether the short-term administration of G-CSF or GM-CSF exerts beneficial effects on atherosclerosis.


RESULTS
Apolipoprotein E-deficient mice were treated with either GM-CSF or G-CSF at a dose of 10 microg x kg(-1) x d(-1) s.c. administered daily for 5 days per week on alternating weeks for a total of 20 doses over an 8-week treatment period. We found that in animals maintained on a high-fat diet, both G-CSF and GM-CSF actually demonstrated an increase in atherosclerotic lesion extent. The increase in atherosclerotic extent was not associated with an increase in either inflammatory cells or expression of proinflammatory genes. Interestingly, adventitial vascularity significantly increased, suggesting a mechanistic role for vasa vasorum neovascularization.


CONCLUSIONS
These findings demonstrate that in this animal model of atherosclerosis, not only did administration of G-CSF or GM-CSF fail to demonstrate any beneficial therapeutic effect, but both resulted in a worsening of atherosclerosis.
Haghighat
Amir
A
Cardiology Division, Emory University School of Medicine, 1639 Pierce Dr, Atlanta, GA 30322, USA.
Weiss
Daiana
D
Whalin
Matthew K
MK
Cowan
D Patrick
DP
Taylor
W Robert
WR
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology*; D004041:Dietary Fats; D004195:Disease Models, Animal; D018450:Disease Progression; D016179:Granulocyte Colony-Stimulating Factor / Q000633:toxicity*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000633:toxicity*; D008297:Male; D051379:Mice; D018345:Mice, Knockout
D001057:Apolipoproteins E; D004041:Dietary Fats; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor