The endothelium: an interface between autoimmunity and atherosclerosis in systemic lupus erythematosus?

Abstract

Patients with systemic lupus erythematosus (SLE) have an increased risk of developing cardiovascular disease (CVD). Traditional risk factors fail to fully explain all of this increased risk. As atherosclerosis is recognized as a chronic inflammatory disease, it has been advocated that persistent inflammatory activity in patients with SLE is the principal mechanism that promotes accelerated atherogenesis. Autoantibodies in SLE might contribute to the pathogenesis of atherosclerosis by causing injury to the endothelium and altering the metabolism of lipoproteins involved in atherogenesis. Circulating immune complexes and anti-endothelial cell antibodies can induce expression of a proinflammatory and proadhesive endothelial cell phenotype. Similarly, antiphospholipid antibodies (aPL) may directly activate the endothelium or, via cross-reactivity with other antigens, interfere with lipoprotein metabolism. Antibodies to oxidized low-density lipoprotein (anti-oxLDL) rise with anti-double-stranded DNA antibody titres, complement activation and disease activity scores in patients with SLE. Both clinical and in vitro studies, however, have yielded conflicting results regarding the role of anti-oxLDL and aPL antibodies in CVD. Elevated levels of antibodies to high-density lipoprotein (HDL) and apolipoprotein A1 (the principal protein fraction of HDL) are found in patients with coronary ischaemia. Titres of these antibodies are significantly higher in SLE patients with persistent inflammatory disease and correlate inversely with activity of paraoxonase, a key enzyme that gives HDL its anti-oxidant properties. This review summarizes the evidence that autoantibodies in SLE might contribute to the pathogenesis of atherosclerosis by causing injury to the endothelium and altering the metabolism of lipoproteins involved in atherogenesis.