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Journal of Lipid Research, Vol. 46, 1081-1092, June 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology
Thematic Review |
Thematic Review Series: The Immune System and Atherogenesis. Cytokines affecting endothelial and smooth muscle cells in vascular disease
* Department of Pathology, University of Washington, Seattle, WA
Department of Pharmacological Sciences, University of Milan, Milan, Italy
Published, JLR Papers in Press, April 16, 2005. DOI 10.1194/jlr.R500004-JLR200
1 To whom correspondence should be addressed. e-mail: ewraines{at}u.washington.edu
The cellular and extracellular matrix accumulations that comprise the lesions of atherosclerosis are driven by local release of cytokines at sites of predilection for lesion formation, and by the specific attraction and activation of cells expressing receptors for these cytokines. Although cytokines were originally characterized for their potent effects on immune and inflammatory cells, they also promote endothelial cell dysfunction and alter smooth muscle cell (SMC) phenotype and function, which can contribute to or retard vascular pathologies.
This review summarizes in vivo studies that have characterized endothelial- and smooth muscle-specific effects of altering cytokine signaling in vascular disease. Although multiple reports have identified cytokines as pivotal players in endothelial and SMC responses in vascular disease, they also have highlighted the need to delineate the critical genes and specific cellular functions regulated by individual cytokine signaling pathways.
Abbreviations: apoE, apoplipoprotein E; CCL, CC chemokine ligand; CCR, CC chemokine receptor; CD40L, CD40 ligand; GRO, growth-related oncogene; ICAM, intercellular adhesion molecule; IFN, interferon; IL, interleukin; IL-1Ra, interleukin-1 receptor antagonist; KC, keratinocyte chemokine; MCP, monocyte chemoattractant protein; MHC, major histocompatibility complex; MIF, macrophage migration inhibitory factor; NF-
B, nuclear factor B; SCID, severe combined immunodeficient; SDF, stromal cell-derived factor; SMC, smooth muscle cell; TGF, transforming growth factor; TNF, tumor necrosis factor; VCAM, vascular cell adhesion molecule
Supplementary key words atherosclerosis • chemokine • injury • adhesion molecule • survival • proliferation • antigen presentation • extracellular matrix • inflammation • signaling
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