Update on cardiovascular disease in lupus

Abstract

Purpose of review: Atherosclerotic cardiovascular disease confers significant morbidity and mortality in patients with systemic lupus erythematosus (SLE) and cannot be fully explained by traditional cardiovascular risk factors. Recent immunologic discoveries have outlined putative pathways in SLE that may also accelerate the development of atherosclerosis.

Recent findings: Aberrant innate and adaptive immune responses implicated in lupus pathogenesis may also contribute to the development of accelerated atherosclerosis in these patients. Defective apoptosis, abnormal lipoprotein function, autoantibodies, aberrant neutrophil responses, and a dysregulated type I interferon pathway likely contribute to endothelial dysfunction. SLE macrophages have an inflammatory phenotype that may drive progression of plaque.

Summary: Recent discoveries have placed increased emphasis on the immunology of atherosclerotic cardiovascular disease. Understanding the factors that drive the increased risk for cardiovascular disease in SLE patients may provide selective therapeutic targets for reducing inflammation and improving outcomes in atherosclerosis.

Figure 1

Potential pathways promoting atherosclerosis in SLE Endothelial dysfunction (ED) may be induced by an imbalance of vascular damage (triggered by innate and adaptive immune stimuli) and impaired vascular repair induced by a dysfunction of endothelial progenitor cells (EPCs) induced by type I IFNs and metabolic dysfunction. Various proinflammatory pathways in the plaque may induce neutrophils to undergo NETosis and promote further inflammatory cell recruitment, induce endothelial cell death, enhance local type I IFN synthesis, oxidize lipoproteins and promote thrombosis. Type I IFNs and other stimuli may promote enhanced foam cell formation. Decrease in B Regulatory cells (BRegs) may promote loss of natural IgM, impaired apoptosis and increased IFNs at the level of the plaque. Platelet activation may lead to acute coronary syndromes.