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Journal of Lipid Research, Vol. 50, S388-S393, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Atherogenesis

The role of innate immunity in atherogenesis¹

Karsten Hartvigsen^*, Meng-Yun Chou^*, Lotte F. Hansen^*, Peter X. Shaw^*, Sotirios Tsimikas^*, Christoph J. Binder^*,, and Joseph L. Witztum^2,*

^* Department of Medicine, University of California, San Diego, CA
CeMM Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria

¹ Guest editor for this article was Linda Curtiss, the Scripps Research Institute.

Published, JLR Papers in Press, December 22, 2008.

² To whom correspondence should be addressed. e-mail: jwitztum{at}ucsd.edu

ABSTRACT

Lipid peroxidation is a common event in health and is greatly accelerated in pro-inflammatory settings such as hypercholesterolemia. Consequently, oxidation-specific epitopes are generated, which are pro-inflammatory and immunogenic, leading to both adaptive and innate responses. Because innate immune mechanisms use conserved germline pattern recognition receptors (PRRs) that are preformed and present at birth, it is not obvious why they should bind to such epitopes. In this review, we put forward the hypothesis that because oxidation-specific epitopes are ubiquitous in both health and disease, and because they in essence represent "danger signals," they constitute a class of pathogen-associated molecular patterns leading to the natural selection of multiple innate PRRs that target such epitopes. We suggest that apoptotic cells, and the blebs and microparticles released from such cells, which are rich in oxidation-specific epitopes and thus pro-inflammatory, constitute an endogenous set of selecting antigens. In turn, natural antibodies, scavenger receptors, and soluble innate proteins, such as pentraxins, all represent PRRs that target such epitopes. We discuss the evidence for this hypothesis and the consequences of such responses in health and disease, such as atherosclerosis.

Supplementary key words oxidation-specific epitopes • natural antibodies • oxidized lipids • oxidized LDL • scavenger receptors

Abbreviations: Ab, antibody; apoB, apolipoprotein B; CRP, C-Reactive Protein; MDA, malondialdehyde; NAb, natural antibody; OxLDL, oxidized LDL; OxPL, oxidized phopholipid; PAMP, pathogen-associated molecular pattern; PC, phosphocholine; POVPC, 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine; PRR, pattern recognition receptor; SR, scavenger receptor

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