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Lupus, Vol. 12, No. 7, 550-554 (2003)
DOI: 10.1191/0961203303lu400oa

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

E Matsuura

Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan, eijimatu{at}md.okayama-u.ac.jp

K Kobayashi

Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

T Koike

Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Y Shoenfeld

Department of Medicine B, and Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel Hashomer, Israel

M A Khamashta

Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, London SE1 7EH, UK

G RV Hughes

Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, London SE1 7EH, UK

ß2-Glycoprotein I (ß2-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 ß2-GPI and anti-ß2-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 ß2-GPI (J Lipid Res 2001; 42: 697; J Lipid Res 2002; 43: 1486). These ß2-GPI ligands provide an electrostatic interaction between oxLDL and ß2-GPI followed by forming stable complexes (such as Schiff base adducts). The -carboxyl function in these ligands is responsible for ß2-GPI binding to oxLDL and the oxLDL-ß2-GPI complexes are anti-ß2-GPI auto-Ab-dependentlytaken up by macrophages (i.e., by phagocytosis). Our recent observations are consistent with the evidence that ß2-GPI co-localizes with lymphocytes and mononuclear cells in human athero-plaques. Thus, autoimmune thrombogenesis (atherogenesis) is linked to interaction of anti-ß2-GPI Abs with the ß2-GPI-oxLDL complexes. We propose an alternative idea, that an immune response against the ß2-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’.

Key Words: antiphospholipidantibody • antiphospholipidsyndrome • atherosclerosis • ß2-glycoprotein I • oxidized LDL


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E Matsuura, K Kobayashi, B. Hurley, and L. Lopez
Atherogenic Oxidized Low-Density Lipoprotein/{beta}2-Glycoprotein I (oxLDL/{beta}2GPI) Complexes in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome
Lupus, July 1, 2006; 15(7): 478 - 483.
[Abstract] [PDF]