Are oxidized LDL/beta2-glycoprotein I complexes pathogenic antigens in autoimmune-mediated atherosclerosis?

Eiji Matsuura,Luis R Lopez

doi:10.1080/10446670410001722186

Abstract

The oxidative modification of low-density lipoprotein (LDL) in the intima of arteries contributes to the initiation and progression of atherosclerotic lesions. We have previously reported that oxidized LDL (oxLDL) interacts with an endogenous plasma protein, β2-glycoprotein I (β2GPI), to form complexes and that the interaction is mediated by oxLDL specific ligands. We have also demonstrated the presence of oxLDL/β2GPI complexes in the blood stream of patients with systemic inflammatory and autoimmune diseases. These findings implicate that oxLDL/β2GPI complexes are possible atherogenic autoantigens. Autoantibodies to oxLDL/β2GPI complexes have been associated with arterial thrombosis. Further, circulating IgG immune complexes containing oxLDL and 2GPI were also detected in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Although many unanswered questions remain about the exact pathogenic mechanism(s) involved, oxLDL/β2GPI complexes may be described as metabolic products relevant in atherogenesis and as significant participants in autoimmune-mediated atherosclerosis.

Highlights

Atherosclerosis is a major health concern of worldwide importance
Oxidized low-density lipoprotein (LDL) is the principal lipoprotein that accumulates within cells of atherosclerotic lesions and it co-localizes with b2-glycoprotein I (b2GPI) (George et al, 1999)
In addition to the oxidative modification of LDL, the action of local soluble mediators of inflammation and chemotactic factors and the accumulation of immune cells in response to various external and/or internal stimuli, an active humoral immune response has been recently incorporated into the process

Summary

INTRODUCTION

Atherosclerosis is a major health concern of worldwide importance. The experimental evidence has established a causal relationship between atherosclerosis and lipoprotein metabolism. The premature occurrence of atherosclerotic lesions associated with significant cardiovascular morbidity and mortality in patients with systemic autoimmune diseases, suggested a contributing role of autoimmunity in the development of atherosclerosis. Oxidized LDL (oxLDL) is the principal lipoprotein that accumulates within cells of atherosclerotic lesions and it co-localizes with b2GPI (George et al, 1999). These findings further suggested the participation of antiphospholipid antibodies in atherogenesis. We review recent new insights into autoimmune-mediated mechanisms on development of atherosclerosis, mostly based on our recent observations and discuss the possible clinical significance of circulating oxLDL/b2GPI complexes and autoantibodies related to these complexes

CURRENT CONCEPTS ON ATHEROGENIC MECHANISMS

MACROPHAGES AND SCAVENGER RECEPTORS

AUTOIMMUNITY AND ATHEROSCLEROSIS

ANTIPHOSPHOLIPID SYNDROME AND ATHEROSCLEROSIS

Findings

CONCLUSION