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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:621.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Granulocyte Macrophage Colony-Stimulating Factor Regulates Dendritic Cell Content of Atherosclerotic Lesions

Zory Shaposhnik; Xuping Wang; Michael Weinstein; Brian J. Bennett; Aldons J. Lusis

From the Department of Molecular and Medical Pharmacology (Z.S.), UCLA School of Medicine, Los Angeles, Calif; the Department of Medicine (X.W., M.W., B.J.B., A.J.L.), Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, and Molecular Biology Institute, UCLA School of Medicine, Los Angeles, Calif.

Correspondence to Aldons J. Lusis, 47-123 CHS, UCLA School of Medicine, Los Angeles, CA 90095-1679. E-mail jlusis{at}mednet.ucla.edu

Objective— Recent evidence suggests that dendritic cells may play an important role in atherosclerosis. Based primarily on previous in vitro studies, we hypothesized that granulocyte macrophage colony-stimulating factor (GM-CSF)-deficient mice would have decreased dendritic cells in lesions.

Methods and Results— To test this, we characterized gene targeted GM-CSF^–/– mice crossed to hypercholesterolemic low-density lipoprotein receptor null mice. Our results provide conclusive evidence that GM-CSF is a major regulator of dendritic cell formation in vivo. Aortic lesion sections in GM-CSF^–/– low-density lipoprotein receptor null animals showed a dramatic 60% decrease in the content of dendritic cells as judged by CD11c staining but no change in the overall content of monocyte-derived cells. The GM-CSF–deficient mice exhibited a significant 20% to 50% decrease in the size of aortic lesions, depending on the location of the lesions. Other prominent changes in GM-CSF^–/– mice were decreased lesional T cell content, decreased autoantibodies to oxidized lipids, and striking disruptions of the elastin fibers adjacent to the lesion.

Conclusion— Given that GM-CSF is dramatically induced by oxidized lipids in endothelial cells, our data suggest that GM-CSF serves to regulate dendritic cell formation in lesions and that this, in turn, influences inflammation, plaque growth and possibly plaque stability.

Recent evidence suggests that dendritic cells may play an important role in atherosclerosis. We hypothesized that granulocyte macrophage colony-stimulating factor (GM-CSF)-deficient mice would have decreased dendritic cells in lesions. Our data suggest that GM-CSF regulates dendritic cell formation in lesions and that this influences plaque growth and stability.

Key Words: atherosclerosis • dendritic cells • elastin • GM-CSF • macrophages

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