Oxidation of LDL and its clinical implication

Eiji Matsuura, Graham R.V. Hughes, Munther A. Khamashta

Research output: Contribution to journalReview article

152 Citations (Scopus)

Abstract

Oxidative modification of low-density lipoprotein (LDL) is one of the earliest events in atherosclerosis. Oxidized LDL (oxLDL) represents a variety of modification of both lipid and apolipoprotein B (apoB) components by lipid peroxidation. This promotes atherosclerosis through inflammatory and immunologic mechanisms that lead to the formation of macrophage foam cells. Recent findings also suggest that oxLDL forms complexes with β2-glycoprotein I (β2GPI) and/or C-reactive protein (CRP) within atherosclerotic lesions and that these complexes appear in the circulation. Autoantibodies (auto-Abs) against oxLDL/β2GPI complexes occur in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). These autoantibodies significantly correlate with arterial thrombosis. IgG auto-Abs having similar specificity emerge spontaneously in NZW × BXSB F1 mice, which generally are considered to be an animal model of APS, and these mice produce a monoclonal IgG auto-Ab (WB-CAL-1) against oxLDL/β2GPI complexes. WB-CAL-1 significantly increased the in vitro uptake of oxLDL/β2GPI complexes by macrophages, which suggests that such IgG auto-Abs are pro-atherogenic. In contrast, IgM anti-oxLDL natural Abs found in the atherosclerosis-prone mice have been proposed to be protective. The presence of such Abs in humans has been documented in many publications but their exact pathophysiological significance remains unclear. In this article, we review recent progress in our understanding of the clinical significance of oxidation of LDL, formation of oxLDL complexes, and Abs in atherosclerotic and/or autoimmune disease.

Original languageEnglish
Pages (from-to)558-566
Number of pages9
JournalAutoimmunity Reviews
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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