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

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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 (RT-PCR) 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.

Original languageEnglish
Pages (from-to)251-257
Number of pages7
JournalDrugs in R and D
Volume9
Issue number4
DOIs
Publication statusPublished - 2008

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Keywords

  • Aminaftone, pharmacodynamics
  • Aminobenzoic acids, pharmacodynamics
  • Vascular disorders

ASJC Scopus subject areas

  • Pharmacology

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