Background The chronic inflammatory nature of systemic lupus erythematosus (SLE) is hypothesized to lead to many co-morbidities including premature accelerated atherosclerosis.
Objectives In this study, we: 1) assessed levels of several classic atherosclerosis related factors in SLE patients, including macrophage migration inhibitory factor (MIF), vascular endothelial growth factor (VEGF) and numbers of peripheral endothelial progenitor cells (EPCs), 2) explored the mechanisms by which SLE causes premature accelerated atherosclerosis, 3) investigated the potential role of artesunate (ART) in ameliorating SLE-associated atherosclerosis.
Methods SLE disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index. VEGF and MIF levels in serum and cultured supernatant were determined by ELISA. Peripheral CD34+KDR+ cells were measured by flow cytometry to represent EPCs. Human umbilical vein endothelial cells (HUVECs) and PBMCs were cultured with or without the presence of 1000 U/ml interferon (IFN)α-1b for 24 hours. To detect the effect of ART on these cells, ART at a dose of 5 or 20 μmol/L was added to the culture system for 12 and 24 hours.
Results SLE patients had high levels of MIF, low levels of VEGF and reduced numbers of EPCs, which were correlated with disease activity and aberrant IFN-inducible gene expressions. In vitro experiments indicated that MIF levels significantly elevated after IFNα treatment, while VEGF levels varied at different time periods by showing a decline after 12 hours stimulation but an incline at 24 hours. ART significantly suppressed IFN-α promoted VEGF and MIF production at 24 hours.
Conclusions ART could modulate atherosclerosis related factors through the inhibition of type I IFN in SLE patients, thus may have therapeutic potential for SLE-associated atherosclerosis.
Disclosure of Interest : None declared
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