Antiphospholipid antibodies and atherosclerosis

β₂-Glycoprotein I (β₂-GPI) is a major antigen for anticardiolipin antibodies (aCL) induced in patients with antiphospholipid syndrome and their antigenic epitopes are cryptic. The epitopes appear on the surface of β₂-GPI molecule only when β₂-GPI interacts with lipid membranes containing negatively charged phospholipids or polyoxygenated polystyrene surface. Our data also indicated that CuSO₄-oxidized low density lipoproteins (oxLDL) are subsequently targeted by β₂-GPI and aCL; however, malonedialdehyde (MDA)-modified LDL were recognized neither by β₂-GPI nor aCL. β₂-GPI binding to LDL was rapidly increased by incubation with CuSO₄. Oxidation of lipoproteins was accompanied with the increment of thiobarbituric acid-reactive substances (TBARS) and denature of apolipoprotein. Ligands on LDL for β₂-GPI seemed to be intermediate oxidative derivatives which were extractable into the chloroform phase by Bligh and Dyer's extraction, but not MDA. Further, immune responses against β₂-GPI, as an anti-atherogenic protein, were demonstrated to induce atherogenic effect in in vitro oxLDL uptake by macrophages.