Drugs in R & D

, Volume 9, Issue 4, pp 251–257 | Cite as

Aminaftone, a Derivative of 4-Aminobenzoic Acid, Downregulates Endothelin-1 Production in ECV304 Cells

An In Vitro Study
  • Raffaella Scorza
  • Alessandro Santaniello
  • Giulia Salazar
  • Stefania Lenna
  • Gualtiero Colombo
  • Flavia Turcatti
  • Lorenzo Beretta
Original Research Article

Abstract

Background and objective: Endothelin-1 (ET-1) plays a central role in the pathogenesis of several vascular diseases. Aminaftone is a drug used for the treatment of capillary disorders but which has a mechanism of action that is not fully understood. We investigated whether aminaftone may exert its effect by interfering with the production of ET-1.

Methods: Human ECV304 endothelial cells were incubated with interleukin-1β (IL-1β) 100 IU/mL with or without the addition of increasing concentrations of aminaftone (2, 4 or 6 μg/mL). ET-1 concentrations in surnatants were quantified by enzyme immunoassay kit at 3, 6 and 12 hours. Pre-pro-endothelin-1 (PPET-1) gene expressions were also analysed by real-time polymerase chain reaction (RTPCR) at the same time points. Endothelin-converting enzyme (ECE) activity was also determined.

Results: Incubation with IL-1β increased concentrations of ET-1 and PPET-1 relative gene expression. Incubation with aminaftone significantly reduced production of ET-1 in a concentration-dependent manner. A strong direct correlation was found between ET-1 concentrations and PPET-1 relative gene expression, but aminaftone did not influence ECE activity.

Conclusion: Aminaftone inhibits ET-1 production in cell cultures by interfering with transcription of the PPET-1 gene. These findings may account for the clinical efficacy of aminaftone in the treatment of capillary disorders and may encourage conduct of further clinical trials.

Keywords

ECV304 Cell Chronic Venous Insufficiency Chronic Venous Insufficiency Cellular Sample Minor Groove Binder Probe 

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Raffaella Scorza
    • 1
  • Alessandro Santaniello
    • 1
  • Giulia Salazar
    • 1
  • Stefania Lenna
    • 1
  • Gualtiero Colombo
    • 2
  • Flavia Turcatti
    • 2
  • Lorenzo Beretta
    • 1
  1. 1.Referral Centre for Systemic Autoimmune DiseasesUniversity of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina ElenaMilanItaly
  2. 2.Division of Internal MedicineUniversity of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina ElenaMilanItaly

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