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Journal of Lipid Research, Vol. 46, 1812-1822, September 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic review series: The Immune System and Atherogenesis. Cytokine regulation of macrophage functions in atherogenesis

Alan Daugherty¹, Nancy R. Webb, Debra L. Rateri and Victoria L. King

Cardiovascular Research Center, Gill Heart Institute, University of Kentucky, Lexington, KY

Published, JLR Papers in Press, July 1, 2005. DOI 10.1194/jlr.R500009-JLR200

¹ To whom correspondence should be addressed. e-mail: alan.daugherty{at}uky.edu

This review will focus on the role of cytokines in the behavior of macrophages, a prominent cell type of atherosclerotic lesions. Once these macrophages have immigrated into the vessel wall, they propagate the development of atherosclerosis by modifying lipoproteins, accumulating intracellular lipids, remodeling the extracellular environment, and promoting local coagulation. The numerous cytokines that have been detected in atherosclerosis, combined with the expression of large numbers of cytokine receptors on macrophages, are consistent with this axis being an important contributor to lesion development. Given the vast literature on cytokine-macrophage interactions, this review will be selective, with an emphasis on the major cytokines that have been detected in atherosclerotic lesions and their effects on properties that are relevant to lesion formation and maturation. There will be an emphasis on the role of cytokines in regulating lipid metabolism by macrophages.

We will provide an overview of the major findings in cell culture and then put these in the context of in vivo studies.

Abbreviations: apoE, apolipoprotein E; GM-CSF, granulocyte macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; LOX-1, lectin-like oxidized low density lipoprotein receptor-1; LRP, low density lipoprotein receptor-related protein; M-CSF, monocyte colony-stimulating factor; MMP, matrix metalloproteinase; SR-A, class A scavenger receptor; SR-BI, scavenger receptor class B type I; TGF, transforming growth factor; TNF, tumor necrosis factor

Supplementary key words lipoprotein • modification • metabolism • matrix • coagulation

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