Atherosclerosis and systemic lupus erythematosus: mechanistic basis of the association

Abstract

As patients with Systemic Lupus Erythematosus (SLE) live longer due to improved therapies and preventive measures, death and disability from cardiovascular events are increasing. Patients with SLE have an increased risk of atherosclerosis that persists even after accounting for traditional cardiac risk factors. Recent studies strongly suggest that the mechanism is due in part to a combination of inflammatory and immune mechanisms. Contributory factors include increased levels of oxidized lipids (such as oxidized LDL and pro-inflammatory HDL), upregulation of adhesion molecules, and upregulation of cytokines such as MCP-1, TNF-alpha, IFN-gamma, IL-1, and IL-12. Autoanitbodies to oxidized lipids and immune complexes may also play a role in the development of atherosclerosis in SLE. As in the pathogenesis of many lupus disease processes, the increased risk of atherosclerosis seen in SLE is likely due to the complex interplay of many of these inflammatory and immune mediators.

Figure 1

Illustration of interaction of LDL, endothelial release of chemokines, entrance of monocytes into artery wall, formation of OxLDL, engulfment of OxLDL by macrophages to form foam cells. HDL interrupt this atherosclerotic process by reverse cholesterol transport by lipoprotein in the HDL and by prevention of oxidation of LDL by anti-oxidative enzymes such as paroxonase in the HDL.