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

Lupus. 2003;12(7):550-4. doi: 10.1191/0961203303lu400oa.

Abstract

Beta2-Glycoprotein I (beta2-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 beta2-GPI and anti-beta2-GPI auto-Abs and that-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 beta2-GPI (J Lipid Re 2001; 42: 697; J Lipid Res 2002; 43: 1486). These beta2-GPI ligands provide an electrostatic interaction between oxLDL and beta2-GPI followed by forming stable complexes (such as Schiff base adducts). The omega-carboxyl function in these ligand is responsible for beta2-GPI binding to oxLDL and the oxLDL-beta2-GPI complexes are anti-beta2-GPI auto-Ab-dependently taken up by macrophages (i.e., by phagocytosis). Our recent observations are consistent with the evidence that beta2-GPI co-localizes with lymphocytes and mononuclear cells in human athero-plaques. Thus, autoimmune thrombogenesis (atherogenesis) is linked to interaction of anti-beta2-GPI Abs with the beta2-GPI-oxLDL complexes. We propose an alternative idea, that an immune response against the beta2-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'.

MeSH terms

  • Antigen-Antibody Complex
  • Antiphospholipid Syndrome / complications
  • Antiphospholipid Syndrome / immunology*
  • Arteriosclerosis / etiology
  • Arteriosclerosis / physiopathology
  • Autoantibodies / immunology
  • Autoimmunity
  • Glycoproteins / immunology
  • Glycoproteins / metabolism
  • Humans
  • Ligands
  • Lipoproteins, LDL / immunology*
  • Lipoproteins, LDL / metabolism
  • Oxidation-Reduction
  • Risk Factors
  • Thrombosis / blood
  • Thrombosis / etiology
  • Thrombosis / immunology*
  • beta 2-Glycoprotein I

Substances

  • Antigen-Antibody Complex
  • Autoantibodies
  • Glycoproteins
  • Ligands
  • Lipoproteins, LDL
  • beta 2-Glycoprotein I
  • oxidized low density lipoprotein