Oxidative modification of low-density lipoprotein and immune regulation of atherosclerosis

• Published in: Progress in lipid research 2006-11, Vol.45 (6), p.466-486
• Main Authors: Matsuura, Eiji, Kobayashi, Kazuko, Tabuchi, Masako, Lopez, Luis R.
• Format: Article
• Language: English
• Subjects: Antibodies - immunology; Antibodies, Antiphospholipid - immunology; Antiphospholipid antibody; Antiphospholipid syndrome; Antiphospholipid Syndrome - immunology; Antiphospholipid Syndrome - metabolism; Atherosclerosis; Atherosclerosis - immunology; Atherosclerosis - metabolism; Atherosclerosis - therapy; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; beta 2-Glycoprotein I - metabolism; C-Reactive Protein - metabolism; Cholesterol - metabolism; Fatty Acids - metabolism; Foam cell formation; Humans; Immunoglobulin G - immunology; Immunoglobulins, Intravenous - administration & dosage; Immunoglobulins, Intravenous - immunology; Lipoproteins, LDL - metabolism; Oxidation-Reduction; Oxidative Stress - immunology; Oxidative Stress - physiology; Oxidized LDL; Phospholipids - metabolism; Receptors, Scavenger - immunology; β 2-glycoprotein I
• ISSN: 0163-7827; 1873-2194
• DOI: 10.1016/j.plipres.2006.05.001

Oxidized low-density lipoprotein (oxLDL) is thought to promote atherosclerosis through complex inflammatory and immunologic mechanisms that lead to lipid dysregulation and foam cell formation. Recent findings suggested that oxLDL forms complexes with β 2-glycoprotein I (β 2GPI) and/or C-reactive protein (CRP) in the intima of atherosclerotic lesions. Autoantibodies against oxLDL/β 2GPI complexes occur in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) and significantly correlate with arterial thrombosis. IgG autoantibodies having similar specificity emerged spontaneously in non-immunized NZW × BXSB F1 mice, an animal model of APS, and a monoclonal autoantibody (WB-CAL-1; IgG2a) against complexed β 2GPI (oxLDL/β 2GPI complexes) was derived from the same mice. WB-CAL-1 significantly increased the in vitro uptake of oxLDL/β 2GPI complexes by macrophages. This observation strongly suggests that such IgG autoantibodies are pro-atherogenic. In contrast, IgM anti-oxLDL natural antibodies found in the atherosclerosis-prone mice ( ApoE -/- and LDL-R -/- mice) have been proposed to be anti-atherogenic (protective). The presence of IgG anti-oxLDL antibodies in humans has been documented in many publications but their exact clinical significance remains unclear. In this article, we review recent progress in our understanding of the mechanisms involved in oxidation of LDL, formation of oxLDL complexes, and antibody mediated-immune regulation of atherogenesis.