POS1414 TYPE I INTERFERONS INDUCE TIE2-MEDIATED ENDOTHELIAL CELL DYSFUNCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS

Background Endothelial cell (EC) dysfunction is a hallmark of Systemic Lupus Erythematosus (SLE) and has been generally accepted to be one the important factors contributing higher risk thrombosis atherosclerotic events observed in SLE patients. Although presence traditional (smoking, diabetes, increased age, obesity) autoantibodies are associated with atherosclerosis thrombotic events, they do not completely explain these SLE, suggesting existence other mechanism/factors. Tie2 tyrosine kinase receptor essential for vascular development blood vessel remodeling through interaction its ligands angiopoietin-1 (Ang-1) Ang-2. In homeostatic conditions, both Ang-1 Ang-2 activate signaling induce stabilization Tie1-dependent manner. However, inflammatory processes Tie1 cleavage, leading inhibition Ang-1-induced activation, increase now acting as antagonist, culminating EC activation [1,2]. Importantly, this process implicated thrombosis. Objectives As type I Interferons (IFN-α IFN-β) key cytokines pathogenesis aim study determine whether signaling-mediated endothelial dysfunction. Methods Serum levels Ang-1, sTie1 patients (n=48) healthy control (HC, n=29) were measured by ELISA. Human Umbilical Vein (HUVEC) stimulated serum (20%), IFN-α IFN-β (1000 IU) 5, 15, 30 min 1, 2, 4, 6, 8, 12, 24, 48 72 hours mRNA protein expression Ang-2, determined quantitative PCR (qPCR) ELISA, respectively. The phosphorylation was Western Blot HUVEC viability calcein assay. angiogenic capacity tube formation Silencing assays performed siRNAs addressed IFNAR1 receptors. Results Type IFNs, mainly IFN-β, significantly reduced TIE1 TIE2 levels. stimulation secretion ectodomain (sTie1). Both IFNs after 24h stimulation. Also, induced at early time points (<4h). Furthermore, (Figure 1). HUVEC. (<1h). We found elevated compared HC. short times (4h) decreased 24h. Remarkably, effect reversed silencing receptors IFNAR1. Figure 1. or IU/ml) indicated points. Means SEM shown. * p<0.05, ** p<0.01 **** p<0.0001. representative immunoblot phosphorilation 24 h Conclusion Our results demonstrate that play relevant role stability cells inhibiting signaling, may cardiovascular References [1]Kim, M. et al . Journal Clinical Investigation 126, 3511–3525 (2016). [2]Saharinen, P., Eklund, L. & Alitalo, K. Nature Reviews Drug Discovery 16, 635–661 (2017). Acknowledgements: NIL. Disclosure Interests None Declared.