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(Circulation. 2007;115:2049-2054.)
© 2007 American Heart Association, Inc.

Vascular Medicine

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; 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.

Correspondence to W. Robert Taylor, MD, PhD, Cardiology Division, Emory University School of Medicine, 1639 Pierce Dr, Ste 319 WMB, Atlanta, GA 30322. E-mail wtaylor{at}emory.edu

Received September 20, 2006; accepted February 20, 2007.

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.

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