Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome

Eiji Matsuura, Kazuko Kobayashi, T. Koike, Y. Shoenfeld, M. A. Khamashta, G. R V Hughes

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

β2-Glycoprotein I (β2-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome (APS). We recently reported that oxidized LDL (oxLDL) is subsequently targeted by β2-GPI and anti-β2-GPI auto-Abs and that ω-carboxyl variants of 7-ketocholesteryl esters, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and 7-ketocholesteryl-12-carboxy (keto) octadodecanoate (oxLig-2), are ligands for β2-GPI (J Lipid Res 2001; 42: 697; J Lipid Res 2002; 43: 1486). These β2-GPI ligands provide an electrostatic interaction between oxLDL and β2-GPI followed by forming stable complexes (such as Schiff base adducts). The ω-carboxyl function in these ligands is responsible for β2-GPI binding to oxLDL and the oxLDL-β2-GPI complexes are anti-β2-GPI auto-Ab-dependently taken up by macrophages (i.e., by phagocytosis). Our recent observations are consistent with the evidence that β2-GPI co-localizes with lymphocytes and mononuclear cells in human athero-plaques. Thus, autoimmune thrombogenesis (atherogenesis) is linked to interaction of anti-β2-GPI Abs with the β2-GPI-oxLDL complexes. We propose an alternative idea, that an immune response against the β2-GPI-oxLDL complexes may be involved in mechanisms in the development of atherosclerosis, which has been explained by the theory of 'the response to injury'.

Original languageEnglish
Pages (from-to)550-554
Number of pages5
JournalLupus
Volume12
Issue number7
DOIs
Publication statusPublished - 2003

Fingerprint

Antiphospholipid Syndrome
Glycoproteins
Thrombosis
Ligands
LDL Lipoproteins
oxidized low density lipoprotein
Atherosclerosis
Anticardiolipin Antibodies
Schiff Bases
Static Electricity
Phagocytosis
Esters

Keywords

  • β2-glycoprotein I
  • Antiphospholipid antibody
  • Antiphospholipid syndrome
  • Atherosclerosis
  • Oxidized LDL

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome. / Matsuura, Eiji; Kobayashi, Kazuko; Koike, T.; Shoenfeld, Y.; Khamashta, M. A.; Hughes, G. R V.

In: Lupus, Vol. 12, No. 7, 2003, p. 550-554.

Research output: Contribution to journalArticle

Matsuura, Eiji ; Kobayashi, Kazuko ; Koike, T. ; Shoenfeld, Y. ; Khamashta, M. A. ; Hughes, G. R V. / Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome. In: Lupus. 2003 ; Vol. 12, No. 7. pp. 550-554.
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abstract = "β2-Glycoprotein I (β2-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome (APS). We recently reported that oxidized LDL (oxLDL) is subsequently targeted by β2-GPI and anti-β2-GPI auto-Abs and that ω-carboxyl variants of 7-ketocholesteryl esters, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and 7-ketocholesteryl-12-carboxy (keto) octadodecanoate (oxLig-2), are ligands for β2-GPI (J Lipid Res 2001; 42: 697; J Lipid Res 2002; 43: 1486). These β2-GPI ligands provide an electrostatic interaction between oxLDL and β2-GPI followed by forming stable complexes (such as Schiff base adducts). The ω-carboxyl function in these ligands is responsible for β2-GPI binding to oxLDL and the oxLDL-β2-GPI complexes are anti-β2-GPI auto-Ab-dependently taken up by macrophages (i.e., by phagocytosis). Our recent observations are consistent with the evidence that β2-GPI co-localizes with lymphocytes and mononuclear cells in human athero-plaques. Thus, autoimmune thrombogenesis (atherogenesis) is linked to interaction of anti-β2-GPI Abs with the β2-GPI-oxLDL complexes. We propose an alternative idea, that an immune response against the β2-GPI-oxLDL complexes may be involved in mechanisms in the development of atherosclerosis, which has been explained by the theory of 'the response to injury'.",
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