Published Online
on April 2, 2007

A more recent version of this article appeared on April 17, 2007

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Submitted on September 20, 2006
Accepted on February 20, 2007

Granulocyte Colony-Stimulating Factor and Granulocyte Macrophage Colony-Stimulating Factor Exacerbate Atherosclerosis in Apolipoprotein E-Deficient Mice

Amir Haghighat MD, Daiana Weiss MD, Matthew K. Whalin PhD, D. Patrick Cowan BS, and W. Robert Taylor MD, PhD^*

From the Cardiology Division, Department of Medicine (A.H., D.W., M.K.W., D.P.C., W.R.T.) and Walter H. Coulter Department of Biomedical Engineering (W.R.T.), Emory University School of Medicine, and Atlanta VA Medical Center (W.R.T.), Atlanta, Ga.

^* To whom correspondence should be addressed. E-mail: wtaylor{at}emory.edu.

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.

Methods and Results--Apolipoprotein E-deficient mice were treated with either GM-CSF or G-CSF at a dose of 10 µg · kg^-1 · d^-1 SC 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.

Key words: adventitia • angiogenesis • arteriosclerosis • atherosclerosis • stem cells

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