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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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

Fingerprint

4-Aminobenzoic Acid
Endothelin-1
Down-Regulation
Interleukin-1
Gene Expression
In Vitro Techniques
aminaftone
Immunoenzyme Techniques
Vascular Diseases
Real-Time Polymerase Chain Reaction
Endothelial Cells
Cell Culture Techniques

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Aminaftone, a Derivative of 4-Aminobenzoic Acid, Downregulates Endothelin-1 Production in ECV304 Cells : An in Vitro Study. / Scorza, Raffaella; Santaniello, Alessandro; Salazar, Giulia; Lenna, Stefania; Colombo, Gualtiero; Turcatti, Flavia; Beretta, Lorenzo.

In: Drugs in R and D, Vol. 9, No. 4, 2008, p. 251-257.

Research output: Contribution to journalArticle

@article{5321e2d6da0b45e79e802fa1a4742cfe,
title = "Aminaftone, a Derivative of 4-Aminobenzoic Acid, Downregulates Endothelin-1 Production in ECV304 Cells: An in Vitro Study",
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.",
keywords = "Aminaftone, pharmacodynamics, Aminobenzoic acids, pharmacodynamics, Vascular disorders",
author = "Raffaella Scorza and Alessandro Santaniello and Giulia Salazar and Stefania Lenna and Gualtiero Colombo and Flavia Turcatti and Lorenzo Beretta",
year = "2008",
doi = "10.2165/00126839-200809040-00005",
language = "English",
volume = "9",
pages = "251--257",
journal = "Drugs in R and D",
issn = "1174-5886",
publisher = "Adis International Ltd",
number = "4",

}

TY - JOUR

T1 - Aminaftone, a Derivative of 4-Aminobenzoic Acid, Downregulates Endothelin-1 Production in ECV304 Cells

T2 - An in Vitro Study

AU - Scorza, Raffaella

AU - Santaniello, Alessandro

AU - Salazar, Giulia

AU - Lenna, Stefania

AU - Colombo, Gualtiero

AU - Turcatti, Flavia

AU - Beretta, Lorenzo

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Aminaftone, pharmacodynamics

KW - Aminobenzoic acids, pharmacodynamics

KW - Vascular disorders

UR - http://www.scopus.com/inward/record.url?scp=46349101227&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46349101227&partnerID=8YFLogxK

U2 - 10.2165/00126839-200809040-00005

DO - 10.2165/00126839-200809040-00005

M3 - Article

C2 - 18588356

AN - SCOPUS:46349101227

VL - 9

SP - 251

EP - 257

JO - Drugs in R and D

JF - Drugs in R and D

SN - 1174-5886

IS - 4

ER -