Atherogenesis
The role of innate immunity in atherogenesis1

https://doi.org/10.1194/jlr.R800100-JLR200Get rights and content
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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.

oxidation-specific epitopes
natural antibodies
oxidized lipids
oxidized LDL
scavenger receptors

Cited by (0)

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

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

Abbreviations

1

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