Bosentan blocks the antiangiogenic effects of sera from systemic sclerosis patients: an in vitro study

Clin Exp Rheumatol. Jul-Aug 2015;33(4 Suppl 91):S148-52. Epub 2015 Jun 19.

Abstract

Objectives: In systemic sclerosis (SSc), clinical evidence has shown that Bosentan may foster the regeneration of the peripheral microcirculatory network. The aim of this study was to verify in vitro the influence of Bosentan on the angiogenic performance of dermal microvascular endothelial cells (MVECs) and its possible capacity to counteract the antiangiogenic effects of SSc sera.

Methods: Healthy dermal MVECs were challenged with Bosentan at different concentrations (0.1 μM, 1 μM, 10 μM) or with sera from patients with diffuse cutaneous SSc (n=8) and healthy subjects (n=8), alone or in combination with Bosentan (10 μM). Cell viability and chemoinvasion were determined by WST-1 and Boyden chamber assays, respectively. Angiogenesis was evaluated by capillary morphogenesis on Matrigel.

Results: Challenge of dermal MVECs with SSc sera induced a significant reduction in angiogenesis (p<0.005 vs. basal condition; p<0.001 vs. healthy sera). The addition of Bosentan could significantly restore angiogenesis in the presence of SSc sera (p<0.01 vs. SSc sera alone). Healthy sera promoted cell viability which was, instead, significantly reduced with SSc sera (p<0.005 vs. healthy sera). The addition of Bosentan to MVECs challenged with SSc sera significantly increased cell viability (p<0.005 vs. SSc sera alone), reaching levels similar to MVECs treated with healthy sera. Co-incubation of MVECs with Bosentan and SSc sera significantly increased chemoinvasion (p<0.005 vs. SSc sera alone) which was inhibited by SSc sera (<0.001 vs. healthy sera).

Conclusions: Bosentan effectively counteracts the antiangiogenic effects of SSc sera on dermal MVECs and fosters the restoration of a proangiogenic environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology*
  • Angiostatic Proteins / blood*
  • Bosentan
  • Case-Control Studies
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Humans
  • Neovascularization, Physiologic / drug effects*
  • Scleroderma, Diffuse / blood*
  • Scleroderma, Diffuse / physiopathology
  • Skin / blood supply*
  • Sulfonamides / pharmacology*

Substances

  • Angiogenesis Inducing Agents
  • Angiostatic Proteins
  • Sulfonamides
  • Bosentan