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

An In Vitro Study

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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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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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Authors and Affiliations

  1. Referral Centre for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via Pace 9, Milan, 20122, Italy

    Raffaella Scorza, Alessandro Santaniello, Giulia Salazar, Stefania Lenna & Lorenzo Beretta

  2. Division of Internal Medicine, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy

    Gualtiero Colombo & Flavia Turcatti

Authors
  1. Raffaella Scorza
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  2. Alessandro Santaniello
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  3. Giulia Salazar
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  4. Stefania Lenna
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  5. Gualtiero Colombo
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  6. Flavia Turcatti
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  7. Lorenzo Beretta
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Correspondence to Raffaella Scorza.

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Scorza, R., Santaniello, A., Salazar, G. et al. Aminaftone, a Derivative of 4-Aminobenzoic Acid, Downregulates Endothelin-1 Production in ECV304 Cells. Drugs R D 9, 251–257 (2008). https://doi.org/10.2165/00126839-200809040-00005

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  • DOI: https://doi.org/10.2165/00126839-200809040-00005

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