Objective: To investigate the role of the angiopoietin (Ang)-Tie system in systemic lupus erythematosus (SLE). Endothelial activation is emerging as a key event for leukocyte recruitment and accelerated atherosclerosis in SLE. Recently, the endothelial specific Ang-Tie ligand-receptor system has been identified as a major regulator of vascular responsiveness to inflammatory stimuli.
Methods: Ang-1 (IRMA) and Ang-2 (ELISA) were measured in sera of 43 patients with SLE and 30 healthy controls. Expression of Ang-2 was studied by immunohistochemistry in biopsies of human lupus nephritis.
Results: Circulating Ang-2 concentrations were increased and concentrations of Ang-1 decreased in patients with active SLE compared to healthy controls. This tendency was still present in inactive SLE, although less pronounced. Individual Ang-2 concentrations correlated well with SLEDAI, proteinuria, dsDNS titer, and sVCAM-1. In a multivariate regression analysis, renal involvement was the only independent predictor for elevated Ang 2. Serum Ang-2 was identified as a strong predictor for disease activity by ROC procedures and regression tree models. Protein expression of Ang-2 was up-regulated in glomeruli of patients with lupus nephritis.
Conclusion: These data indicate that Ang-2 mediated disruption of protective Ang 1/Tie2 signaling is operational in SLE. Ang-2 might facilitate endothelial inflammation, permeability and contribute to premature atherosclerosis. Furthermore, circulating Ang-2 may be a valuable new biomarker for disease activity in SLE. Strategies to control the deleterious effects of Ang-2 may open new perspectives to prevent endothelial inflammation in SLE.
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