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01.07.2008 | Original Research Article

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

An In Vitro Study

verfasst von: Dr Raffaella Scorza, Alessandro Santaniello, Giulia Salazar, Stefania Lenna, Gualtiero Colombo, Flavia Turcatti, Lorenzo Beretta

Erschienen in: Drugs in R&D | Ausgabe 4/2008

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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 (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.

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Titel: Aminaftone, a Derivative of 4-Aminobenzoic Acid, Downregulates Endothelin-1 Production in ECV304 Cells
An In Vitro Study
verfasst von: Dr Raffaella Scorza
Alessandro Santaniello
Giulia Salazar
Stefania Lenna
Gualtiero Colombo
Flavia Turcatti
Lorenzo Beretta
Publikationsdatum: 01.07.2008
Verlag: Springer International Publishing
Erschienen in: Drugs in R&D / Ausgabe 4/2008
Print ISSN: 1174-5886
Elektronische ISSN: 1179-6901
DOI: https://doi.org/10.2165/00126839-200809040-00005

Springer Medizin

Abstract

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