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Dual endothelin receptor antagonists contrast the effects induced by endothelin-1 on cultured human microvascular endothelial cells.
Soldano, Stefano; Paolino, Sabrina; Pizzorni, Carmen; Trombetta, Amelia Chiara; Montagna, Paola; Brizzolara, Renata; Corallo, Claudio; Giordano, Nicola; Sulli, Alberto; Cutolo, Maurizio.
Afiliação
  • Soldano S; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, Italy.
  • Paolino S; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, Italy.
  • Pizzorni C; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, Italy.
  • Trombetta AC; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, Italy.
  • Montagna P; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, Italy.
  • Brizzolara R; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, Italy.
  • Corallo C; Department of Medicine, Surgery and Neurosciences, Scleroderma Unit, University of Siena, Italy.
  • Giordano N; Department of Medicine, Surgery and Neurosciences, Scleroderma Unit, University of Siena, Italy.
  • Sulli A; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, Italy.
  • Cutolo M; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, Italy. mcutolo@unige.it.
Clin Exp Rheumatol ; 35(3): 484-493, 2017.
Article em En | MEDLINE | ID: mdl-28134077
OBJECTIVES: To evaluate the ability of dual endothelin (ET) receptor antagonists (ETA/ETB -ETA/BRAs) to contrast the ET-1-induced effects on cultured human microvascular endothelial cells (HMVECs). METHODS: Some cultured HMVECs were untreated, or treated with ET-1 (100nM) or transforming growth factor ß1 (TGFß1, 10ng/mL) alone for 6 days, in order to induce the endothelial-to-mesenchymal transition (EndoMT). Other cultured HMVECs were pre-treated for 1hr with ETA/BRAs bosentan (10µM) or macitentan (1µM, 10µM) before the stimulation with ET-1 for 6 days. At the end of treatments, a mechanical injury was induced to cultured HMVECs (by scratching the cell monolayer with a sterile tip), and then the cell ability to re-fill the damaged area was determined after 24hrs. EndoMT phenotype markers and monocyte chemoattractant protein-1 (MCP-1) were evaluated by qRT-PCR and Western blotting. Statistical analysis was performed using Mann-Whitney-U non-parametric test. RESULTS: Both ET-1 and TGFß1 induced EndoMT and the MCP-1 over-expression in cultured HMVECs, as well as reduced the process of endothelial cell damage repair. Pre-treatment with ETA/BRAs let cultured HMVECs to significantly restore the in vitro damage of the cell monolayer and antagonised the EndoMT process as well as the MCP-1 over-expression (range p<0.05 - p<0.001). Conversely, untreated or TGFß1-treated HMVECs were found unaffected by the ETA/BRAs treatments. CONCLUSIONS: The treatment with dual ETA/BRAs seems to partially restore the altered cell function induced by ET-1 in cultured endothelial cells, and might justify their therapeutic efficiency in clinical conditions characterised by increased concentrations of ET-1.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article