Atherosclerosis in autoimmune diseases.
Lipid peroxidation occurs frequently in patients with systemic autoimmune diseases and contributes to autoimmune vascular inflammation. Oxidized low-density lipoprotein (oxLDL) interacts with beta2-glycoprotein I (beta2GPI), forming oxLDL/beta2GPI complexes. Circulating oxLDL/beta2GPI complexes and autoantibodies to these complexes have been demonstrated in patients with systemic lupus erythematosus and antiphospholipid syndrome. These findings suggest an immunogenic nature of the complexes and an active proatherogenic role in autoimmunity. Biochemical characterization of the complexes and immunohistochemical studies of atherosclerotic lesions suggest that most of the complexes originate in the arterial wall and are released into circulation. The in vitro macrophage uptake of oxLDL/beta2GPI complexes increased significantly in the presence of antiphospholipid antibodies (anti-beta2GPI), suggesting that macrophage Fcgamma receptors are involved in the lipid intracellular influx that leads to foam cell formation. These findings provide an immunologic explanation for the accelerated development of atherosclerosis seen in systemic lupus erythematosus and antiphospholipid syndrome.
Matsuura
Eiji
E
Department of Cell Chemistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan. eijimatu@md.okayama-u.ac.jp
Kobayashi
Kazuko
K
Lopez
Luis R
LR
D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D050197:Atherosclerosis / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress; D053482:beta 2-Glycoprotein I / Q000097:blood / Q000276:immunology
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein