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.
Aminaftone, a derivative of 4-aminobenzoic acid, downregulates endothelin-1 production in ECV304 Cells : an in vitro study / R. Scorza, A. Santaniello, G. Salazar, S. Lenna, G. Colombo, F. Turcatti, L. Beretta. - In: DRUGS IN R&D. - ISSN 1174-5886. - 9:4(2008), pp. 251-257.
|Titolo:||Aminaftone, a derivative of 4-aminobenzoic acid, downregulates endothelin-1 production in ECV304 Cells : an in vitro study|
SCORZA, RAFFAELLA (Primo)
SANTANIELLO, ALESSANDRO (Secondo)
TURCATI, FLAVIA (Penultimo)
BERETTA, LUCA (Ultimo)
|Parole Chiave:||Aminaftone, pharmacodynamics; Aminobenzoic acids, pharmacodynamics; Vascular disorders|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||2008|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.2165/00126839-200809040-00005|
|Appare nelle tipologie:||01 - Articolo su periodico|