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The Tie2 receptor antagonist Angiopoietin-2 facilitates vascular inflammation in Systemic Lupus Erythematosus
  1. Philipp Kümpers (kuempers.philipp{at}mh-hannover.de)
  1. Department of Nephrology, Medical School Hannover, Germany
    1. Sascha David (david.sascha{at}mh-hannover.de)
    1. Department of Nephrology, Medical School Hannover, Germany
      1. Marion Haubitz (haubitz.marion{at}mh-hannover.de)
      1. Department of Nephrology, Medical School Hannover, Germany
        1. Julian Hellpap
        1. Department of Nephrology, Medical School Hannover, Germany
          1. Rüdiger Horn
          1. Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Germany
            1. Verena Bröcker
            1. Institute for Pathology, Medical School Hannover, Germany
              1. Mario Schiffer
              1. Department of Nephrology, Medical School Hannover, Germany
                1. Hermann Haller
                1. Department of Nephrology, Medical School Hannover, Germany
                  1. Torsten Witte (witte.torsten{at}mh-hannover.de)
                  1. Department of Rheumatology and Immunology, Medical School Hannover, Germany

                    Abstract

                    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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