Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells

Giulia Salazar, Chiara Bellocchi, Katia Todoerti, Federica Saporiti, Luca Piacentini, Raffaella Scorza, Gualtiero Colombo

Research output: Contribution to journalArticle

Abstract

Aminaphtone, a drug used in the treatment of chronic venous insufficiency (CVI), showed a remarkable role in the modulation of several vasoactive factors, like endothelin-1 and adhesion molecules. We analysed in vitro the effects of Aminaphtone on whole-genome gene expression and production of different inflammatory proteins. ECV-304 endothelial cells were stimulated with IL-1β 100 U/ml in the presence or absence of Aminaphtone 6 μg/ml. Gene expression profiles were compared at 1, 3, and 6 h after stimulation by microarray. Supernatants of ECV-304 cultures were analysed at 3, 6, 12, and 24 h by multiplex ELISA for production of several cytokine and chemokines. Microarrays showed a significant down-regulation at all times of a wide range of inflammatory genes. Aminaphtone appeared also able to modulate the regulation of immune response process (down-regulating cytokine biosynthesis, transcripts involved in lymphocyte differentiation and cell proliferation, and cytokine-cytokine receptor interaction) and to regulate genes engaged in homeostasis, secretion, body fluid levels, response to hypoxia, cell division, and cell-to-cell communication and signalling. Results were confirmed and extended analysing the secretome, which showed significant reduction of the release of 14 cytokines and chemokines. These effects are predicted to be mediated by interaction with different transcription factors. Aminaphtone was able to modulate the expression of inflammatory molecules relevant to the pathogenesis of several conditions in which the endothelial dysfunction is the main player and early event, like scleroderma, lung fibrosis, or atherosclerosis.

Original languageEnglish
Pages (from-to)59-69
Number of pages11
JournalEuropean Journal of Pharmacology
Volume782
DOIs
Publication statusPublished - Jul 5 2016

Keywords

  • Cytokines
  • Endothelial cells
  • Endothelin-1
  • Gene expression profiling
  • Inflammation

ASJC Scopus subject areas

  • Pharmacology

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