Figure 2.

The interplay of various inflammatory mediators increases vascular damage and plaque formation in systemic lupus erythematosus. IFN-α contributes to endothelial dysfunction and decreased repair of endothelial damage by decreasing numbers and function of endothelial progenitor cells (EPCs) and circulating angiogenic cells (CACs). In addition to synthesizing type I IFNs, low density granulocytes (LDGs) present in systemic lupus erythematosus patients are directly toxic to the endothelium. Altered lipid profiles secondary to abnormal chylomicron processing, increased pro-inflammatory high density lipoprotein (pi-HDL) and increased oxidized low density lipoprotein (ox-LDL) also promote atherosclerosis development. The abnormal redox environment in systemic lupus erythematosus also promotes endothelial dysfunction and modulates lipid profiles. Antibodies to lipoproteins or endothelial targets may also contribute to vascular damage. Cytokines such as TNF-α, IL-17 and IFN-γ may also have pro-atherogenic effects on blood vessels. The combination of some or all of these factors in an individual patient results in endothelial dysfunction, increased plaque burden and an increased risk of cardiovascular events. IC, immune complex; PDC, plasmacytoid dendritic cell; RNS, reactive nitrogen species; ROS, reactive oxygen species.