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Circulating oxidized LDL forms complexes with β2-glycoprotein I: implication as an atherogenic autoantigen
- Source :
- Journal of Lipid Research, Vol 44, Iss 4, Pp 716-726 (2003)
- Publication Year :
- 2003
- Publisher :
- Elsevier, 2003.
-
Abstract
- β2-glycoprotein I (β2-GPI) is a major antigen for antiphospholipid antibodies (Abs, aPL) present in patients with antiphospholipid syndrome (APS). We recently reported (J. Lipid Res., 42: 697, 2001; J. Lipid Res., 43: 1486, 2002) that β2-GPI specifically binds to Cu2+-oxidized LDL (oxLDL) and that the β2-GPI ligands are ω-carboxylated 7-ketocholesteryl esters. In the present study, we demonstrate that oxLDL forms stable and nondissociable complexes with β2-GPI in serum, and that high serum levels of the complexes are associated with arterial thrombosis in APS. A conjugated ketone function at the 7-position of cholesterol as well as the ω-carboxyl function of the β2-GPI ligands was necessary for β2-GPI binding. The ligand-mediated noncovalent interaction of β2-GPI and oxLDL undergoes a temperature- and time-dependent conversion to much more stable but readily dissociable complexes in vitro at neutral pH. In contrast, stable and nondissociable β2-GPI-oxLDL complexes were frequently detected in sera from patients with APS and/or systemic lupus erythematodes. Both the presence of β2-GPI-oxLDL complexes and IgG Abs recognizing these complexes were strongly associated with arterial thrombosis. Further, these same Abs correlated with IgG immune complexes containing β2-GPI or LDL.Thus, the β2-GPI-oxLDL complexes acting as an autoantigen are closely associated with autoimmune-mediated atherogenesis.
- Subjects :
- antiphospholipid syndrome
arterial thrombosis
autoantibody
Biochemistry
QD415-436
Subjects
Details
- Language :
- English
- ISSN :
- 00222275
- Volume :
- 44
- Issue :
- 4
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Lipid Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.0164a5f6c85e4caebf18c4d8e4410e83
- Document Type :
- article
- Full Text :
- https://doi.org/10.1194/jlr.M200329-JLR200