The role of innate immunity in atherogenesis.

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.

journal_name

J Lipid Res

authors

Hartvigsen K,Chou MY,Hansen LF,Shaw PX,Tsimikas S,Binder CJ,Witztum JL

doi

10.1194/jlr.R800100-JLR200

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

S388-93

eissn

0022-2275

issn

1539-7262

pii

R800100-JLR200

journal_volume

50 Suppl

pub_type

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