Oxidative modification of low-density lipoprotein and immune regulation of atherosclerosis

Eiji Matsuura, Kazuko Kobayashi, Masako Tabuchi, Luis R. Lopez

Research output: Contribution to journalReview article

130 Citations (Scopus)

Abstract

Oxidized low-density lipoprotein (oxLDL) is thought to promote atherosclerosis through complex inflammatory and immunologic mechanisms that lead to lipid dysregulation and foam cell formation. Recent findings suggested that oxLDL forms complexes with β2-glycoprotein I (β2GPI) and/or C-reactive protein (CRP) in the intima of atherosclerotic lesions. Autoantibodies against oxLDL/β2GPI complexes occur in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) and significantly correlate with arterial thrombosis. IgG autoantibodies having similar specificity emerged spontaneously in non-immunized NZW × BXSB F1 mice, an animal model of APS, and a monoclonal autoantibody (WB-CAL-1; IgG2a) against complexed β2GPI (oxLDL/β2GPI complexes) was derived from the same mice. WB-CAL-1 significantly increased the in vitro uptake of oxLDL/β2GPI complexes by macrophages. This observation strongly suggests that such IgG autoantibodies are pro-atherogenic. In contrast, IgM anti-oxLDL natural antibodies found in the atherosclerosis-prone mice (ApoE-/- and LDL-R-/- mice) have been proposed to be anti-atherogenic (protective). The presence of IgG anti-oxLDL antibodies in humans has been documented in many publications but their exact clinical significance remains unclear. In this article, we review recent progress in our understanding of the mechanisms involved in oxidation of LDL, formation of oxLDL complexes, and antibody mediated-immune regulation of atherogenesis.

Original languageEnglish
Pages (from-to)466-486
Number of pages21
JournalProgress in Lipid Research
Volume45
Issue number6
DOIs
Publication statusPublished - Nov 1 2006

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Keywords

  • Antiphospholipid antibody
  • Antiphospholipid syndrome
  • Atherosclerosis
  • Foam cell formation
  • Oxidized LDL
  • β-glycoprotein I

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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