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

Abstract

β2-Glycoprotein I (β2-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipidsyndrome (APS). We recently reported that oxidized LDL (oxLDL) is subsequently targeted by β2-GPI and anti-β2-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 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 -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-dependentlytaken 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’.

Keywords

antiphospholipidantibody antiphospholipidsyndrome atherosclerosis β2-glycoprotein I oxidized LDL

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References

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