Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome.
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'.
Matsuura
E
E
Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. eijimatu@md.okayama-u.ac.jp
Kobayashi
K
K
Koike
T
T
Shoenfeld
Y
Y
Khamashta
M A
MA
Hughes
G R V
GR
D000936:Antigen-Antibody Complex; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology*; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism; D010084:Oxidation-Reduction; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000276:immunology*; D053482:beta 2-Glycoprotein I
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D006023:Glycoproteins; D008024:Ligands; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein