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- Title
Aminaftone, a Derivative of 4-Aminobenzoic Acid, Downregulates Endothelin-1 Production in ECV304 Cells: An In Vitro Study.
- Authors
Scorza, Raffaella; Santaniello, Alessandro; Salazar, Giulia; Lenna, Stefania; Colombo, Gualtiero; Turcatti, Flavia; Beretta, Lorenzo
- 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.
- Subjects
AMINOBENZOIC acid derivatives; ENDOTHELINS regulation; ENDOTHELIAL cells; INTERLEUKIN-1; GENETIC transcription; TREATMENT of vascular diseases; CAPILLARIES
- Publication
Drugs in R&D, 2008, Vol 9, Issue 4, p251
- ISSN
1174-5886
- Publication type
Article
- DOI
10.2165/00126839-200809040-00005