Autoantibody-mediated atherosclerosis.
Beta2-glycoprotein I (beta2-GPI) is a major antigen for antiphospholipid antibodies (aPL) present in patients with antiphospholipid syndrome (APS). Oxidized low-density lipoprotein (oxLDL) is subsequently targeted by beta2-GPI and anti-beta2-GPI autoantibodies. Ligands specific for beta2-GPI derived from oxLDL have been characterized as oxidized forms of cholesteryl linoleate, such as 7-ketocholesterol-9-carboxynonanoate, i.e. 9-oxo-9-(7-ketocholest-5-en-3beta-yloxy) nonanoic acid, (namely oxLig-1). The in vitro phenomenon that it is significantly increased in binding of oxLig-1 containing liposomes to macrophages via an interaction with beta2-GPI and an anti-beta2-GPI autoantibody (via the Fcgamma receptor) may propose a novel mechanism on 'autoantibody-mediated atherosclerosis'. Furthermore, autoantibodies against a complex of beta2-GPI and oxLig-1 are detected in sera of APS patients and appearance of the antibodies is associated with episodes of thrombosis, especially, arterial thrombosis. Thus, autoimmune atherogenesis linked to beta2-GPI interaction with oxLDL and autoantibodies may be present in APS.
Matsuura
Eiji
E
Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. eijimatu@md.okayama-u.ac.jp
Kobayashi
Kazuko
K
Koike
Takao
T
Shoenfeld
Yehuda
Y
D017152:Antibodies, Antiphospholipid / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000209:etiology / Q000276:immunology; D001161:Arteriosclerosis / Q000209:etiology* / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism; D008955:Models, Cardiovascular; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D006023:Glycoproteins; D008024:Ligands; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein