Immune responses to oxidative neoepitopes on LDL and phospholipids modulate the development of atherosclerosis.
Extensive evidence suggests that humoral and cellular immune responses against lipid peroxidation products occur in vivo and that they modulate the progression of atherosclerosis. The biological significance of these immune responses is the focus of this review. Lipid peroxidation generates reactive aldehydes and oxidized phospholipids which form complex, immunogenic adducts with proteins or other phospholipids. Autoantibodies against oxidative neoepitopes are present in humans and other species and their titre may be an indicator of the extent of atherosclerosis. Interventions boosting immune responses to oxidized LDL reduce the progression of atherosclerosis in animal models. However, other interventions inhibiting immune cells or signalling factors enhance atherogenesis, suggesting that different elements of the immune system exert opposite effects. Evaluation of the role of immune mechanisms in atherosclerosis is further complicated by the fact that other chronic inflammatory conditions induce similar humoral immune responses to oxidative neoepitopes, in particular oxidized phospholipids. Naturally occurring antibodies cloned from atherosclerotic mice provide insights into the nature of antigens formed in vivo and on biological effects of some antibody populations. For example, antibodies to oxidized phospholipid adducts inhibit macrophage uptake of oxidized LDL by blocking scavenger receptors. Antibodies to oxidation-specific epitopes may also be suitable for non-invasive diagnosis of atherosclerosis.
Palinski
W
W
Department of Medicine, University of California San Diego, La Jolla, California, USA. wpalinski@ucsd.edu
Witztum
J L
JL
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D008078:Cholesterol, LDL / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D015227:Lipid Peroxidation / Q000276:immunology*; D010743:Phospholipids / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D008078:Cholesterol, LDL; D000939:Epitopes; D010743:Phospholipids