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Reduced circulating levels of angiotensin-(1–7) in systemic sclerosis: a new pathway in the dysregulation of endothelial-dependent vascular tone control
  1. Alberto Pignone1,
  2. Angela Del Rosso1,
  3. K Bridget Brosnihan2,
  4. Federico Perfetto1,
  5. Riccardo Livi1,
  6. Ginevra Fiori1,
  7. Serena Guiducci1,
  8. Marina Cinelli1,
  9. Veronica Rogai1,
  10. Alessio Tempestini1,
  11. Francesca Bartoli1,
  12. Sergio Generini1,
  13. Carlos M Ferrario2,
  14. Marco Matucci Cerinic1
  1. 1
    Department of Medicine and Surgery, Division of Medicine I and II and Rheumatology, Villa Monna Tessa, University of Florence, Florence, Italy
  2. 2
    Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
  1. A Del Rosso, Department of Medicine and Surgery, Section of Medicine and Rheumatology, University of Florence, viale G. Pieraccini 18, 50134, Florence, Italy; a.delrosso{at}alice.it

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 ACE and neutral endopeptidase (NEP) 24.11, 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 patients with SSc, circulating levels of Ang I, Ang II and Ang-(1–7), with their metabolising enzymes ACE and NEP, and levels of NO and PGI2, and to correlate them to the main characteristics of SSc.

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

Results: Plasma Ang I, Ang II and Ang-(1–7) levels were lower in patients with 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 patients with SSc than in controls were confirmed (p<0.001), while no difference was found for Ang II levels. In patients with 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 patients with SSc than in controls (p<0.05 in all cases).

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

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

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Footnotes

  • Competing interests: None declared.

  • AP and ADR contributed equally to the results of this study.

  • Abbreviations:
    Ang I
    angiotensin I
    Ang II
    angiotensin II
    Ang-(1–7)
    angiotensin-(1–7)
    BK
    bradykinin
    dSSc
    diffuse systemic sclerosis
    EC
    endothelial cell
    lSSc
    limited systemic sclerosis
    NEP
    neutral endopeptidase
    NO
    nitric oxide
    PGF1α
    prostaglandin F1α
    PGI2
    prostaglandin I2
    RAS
    renin–angiotensin system
    SP
    substance P
    SSc
    systemic sclerosis

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