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Reduced circulating levels of angiotensin¡V(1-7) in systemic sclerosis: a new pathway in the dysregulation of endothelial dependent vascular tone control
  1. Alberto Pignone (pignone{at}unifi.it)
  1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy
    1. Angela Del Rosso (a.delrosso{at}alice.it)
    1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy
      1. K Bridget Brosnihan (bbrosnih{at}wfubmc.edu)
      1. Hypertension and Vascular Disease Center, Wake Forest Univ School of Medicine, Winston Salem, NC, United States
        1. Federico Perfetto (perfetto{at}unifi.it)
        1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy
          1. Riccardo Livi (rlivi{at}unifi.it)
          1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy
            1. Ginevra Fiori (ginevrafiori{at}hotmail.com)
            1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy
              1. Serena Guiducci (serena16{at}libero.it)
              1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy
                1. Marina Cinelli (marina.ely{at}libero.it)
                1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy
                  1. Veronica Rogai (laboratorio.matucci{at}unifi.it)
                  1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy
                    1. Alessio Tempestini (alessio_tempestini{at}hotmail.com)
                    1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy
                      1. Francesca Bartoli
                      1. University of Florence, Italy
                        1. Sergio Generini (generini{at}hotmail.com)
                        1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy
                          1. Carlos M Ferrario (cferrari{at}wfubmc.edu)
                          1. Hypertension and Vascular Disease Center, Wake Forest Univ School of Medicine, Winston Salem, NC, United States
                            1. Marco Matucci Cerinic (cerinic{at}unifi.it)
                            1. Dpt Medicine and Surgery, Sect of Medicine and Rheumatology, Univ of Florence, Florence, Italy

                              Abstract

                              Objective: Systemic sclerosis (SSc) impairs endothelium-dependent vasodilatation. Among angiotensin I (Ang I) derived compounds, vasoconstrictor angiotensin II (Ang II) and vasodilator angiotensin-(1-7) [Ang-(1- 7)], cleaved from angiotensin converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP), respectively, play an important role in vascular tone regulation. Ang- (1-7) may act independently or by activating other vasodilating molecules, such as nitric oxide (NO) or prostaglandin I2 (PGI2). Our aim was to assess, in SSc patients, circulating levels of Ang I, Ang II, and Ang-(1-7), with their metabolising enzymes ACE and NEP, and levels of NO, PGI2 and to correlate them to the main characteristics.

                              Methods: Levels of Ang I, Ang II, Ang-(1-7), NEP, ACE, NO, and PGI2 were measured in 32 SSc patients, also assessed for humoral and clinical characteristics, and 55 controls.

                              Results: Plasma Ang I , Ang II and Ang-(1-7) levels were lower in SSc than in controls (p<0.001in all cases). When Ang II and Ang-(1-7) levels were expressed as a function of the available Ang I, lower Ang-(1-7) levels in SSc than in controls were confirmed (p<0.001), while no difference was found for Ang II levels. In SSc, the Ang II/Ang-(1-7) ratio indicated a prevalence of Ang II over Ang-(1-7), while in controls Ang-(1-7) was prevalent (p<0.001). Levels of ACE, NEP, NO and PGI2 were lower in SSc than in controls (p<0.05 in all cases).

                              Conclusion: In SSc, prevalence of the vasoconstricting Ang II over vasodilator Ang-(1-7) suggests a dysfunction of angiotensin-derived cascade that may contribute to dysregulation of the vascular tone.

                              • angiotensin (1-7)
                              • angiotensin converting enzyme
                              • endothelium
                              • neutral endopeptidase
                              • systemic sclerosis

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