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Bosentan regulates the expression of adhesion molecules on circulating T cells and serum soluble adhesion molecules in systemic sclerosis-associated pulmonary arterial hypertension
  1. Florenzo Iannone (f.iannone{at}reumbari.uniba.it)
  1. DIMIMP, Rheumatology Unit, University of Bari, Italy
    1. M Teresa Riccardi (mt.riccardi{at}libero.it)
    1. DIMIMP, Rheumatology Unit, University of Bari, Italy
      1. Serena Guiducci (serena16{at}libero.it)
      1. SOD Internal Medicine 1 and Rheumatology, AOUC Careggi, University of Florence, Italy
        1. Rita Bizzoca (r.bizzoca{at}reumbari.uniba.it)
        1. DIMIMP, Rheumatology Unit, University of Bari, Italy
          1. Marina Cinelli (labmatucci{at}unifi.it)
          1. SOD Internal Medicine 1 and Rheumatology, AOUC Careggi, University of Florence, Italy
            1. Marco Matucci-Cerinic (cerinic{at}unifi.it)
            1. SOD Internal Medicine 1 and Rheumatology, AOUC Careggi, University of Florence, Italy
              1. Giovanni Lapadula (g.lapadula{at}reumbari.uniba.it)
              1. DIMIMP, Rheumatology Unit, University of Bari, Italy

                Abstract

                Objectives: To study the expression of adhesion molecules in Systemic Sclerosis (SSc) patients with and without pulmonary arterial hypertension (PAH) and the effects of therapy with the endothelin-1 (ET-1) receptor antagonist, bosentan.

                Methods: Thirty-five SSc patients and 25 healthy donors (HD) were selected for this study. Ten of 35 patients had isolated PAH assessed by Doppler echocardiography and treated with bosentan. PB lymphocytes were isolated by density gradient centrifugation, and the expression of LFA-1, VLA-4, L-selectin on CD3 T cells was assessed by double immunofluorescence and flow-cytometry. As endothelial activation markers, serum soluble P-selectin, PECAM, VCAM-1, ICAM-1, and vWF antigen were assessed by ELISA. In SSc-PAH patients, T cell subsets and soluble endothelial markers were assessed at baseline and after 6 and 12 months of bosentan therapy.

                Results: In SSc-PAH patients, serum soluble ICAM-1, VCAM-1, P-selectin, and PECAM levels were higher than in HD at baseline and fell to normal values after 12 months of bosentan therapy. CD3-LFA1 T cells were significantly higher in PAH-SSc at baseline than in HD or SSc and significantly decreased after therapy. CD3-Lselectin T cells were significantly lower in SSc-PAH at baseline than in HD or SSc and rose to normal levels after bosentan therapy.

                Conclusions: This study confirms that endothelial activation occurs in SSc, and suggests that changes in the T-cell/endothelium interplay take place in SSc-associated PAH. Bosentan seems to be able to hamper these changes and restore T cell functions in these patients.

                • ICAM-1
                • L-selectin
                • LFA-1
                • VCAM-1
                • VLA-4

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