Research ArticleArticle
The Endothelial-mesenchymal Transition in Systemic Sclerosis Is Induced by Endothelin-1 and Transforming Growth Factor-β and May Be Blocked by Macitentan, a Dual Endothelin-1 Receptor Antagonist
Paola Cipriani, Paola Di Benedetto, Piero Ruscitti, Daria Capece, Francesca Zazzeroni, Vasiliki Liakouli, Ilenia Pantano, Onorina Berardicurti, Francesco Carubbi, Gianluca Pecetti, Stefano Turricchia, Edoardo Alesse, Marc Iglarz and Roberto Giacomelli
The Journal of Rheumatology August 2015, jrheum.150088; DOI: https://doi.org/10.3899/jrheum.150088
Paola Cipriani
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Paola Di Benedetto
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Piero Ruscitti
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Daria Capece
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Francesca Zazzeroni
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Vasiliki Liakouli
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Ilenia Pantano
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Onorina Berardicurti
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Francesco Carubbi
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Gianluca Pecetti
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Stefano Turricchia
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Edoardo Alesse
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Marc Iglarz
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
Roberto Giacomelli
From the Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, and the Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila, L’Aquila; Medical and Scientific Direction, Actelion Pharmaceuticals Italy, Imola, Italy; Drug Discovery Department, Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Supported by FIRA (Fondazione Italiana Ricerca per l’Artrite) 2009. G. Pecetti, S. Turricchia, and M. Iglarz are employees of Actelion Pharmaceuticals Ltd. P. Cipriani received a research grant from Actelion. P. Cipriani, MD, PhD; P. Di Benedetto, PhD; P. Ruscitti, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; D. Capece, PhD; F. Zazzeroni, PhD, Department of Applied Clinical Sciences and Biotechnology, General Phatology Unit, University of L’Aquila; V. Liakouli, MD, PhD; I. Pantano, MD; O. Berardicurti, MD; F. Carubbi, MD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila; G. Pecetti, MD; S. Turricchia, MD, Medical and Scientific Direction, Actelion Pharmaceuticals Italy; E. Alesse, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, General Pathology Unit, University of L’Aquila; M. Iglarz, PhD, Drug Discovery Department, Actelion Pharmaceuticals Ltd.; R. Giacomelli, MD, PhD, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila. Address correspondence Dr. P. Cipriani, Department of Applied Clinical Sciences and Biotechnology, Rheumatology Unit, School of Medicine, University of L’Aquila, Delta 6 Building, Via dell’Ospedale, 67100 L’Aquila, Italy. E-mail: paola.cipriani@cc.univaq.it. Accepted for publication June 19, 2015.
In this issue
The Journal of Rheumatology
Vol. 51, Issue 4
1 Apr 2024
The Endothelial-mesenchymal Transition in Systemic Sclerosis Is Induced by Endothelin-1 and Transforming Growth Factor-β and May Be Blocked by Macitentan, a Dual Endothelin-1 Receptor Antagonist
Paola Cipriani, Paola Di Benedetto, Piero Ruscitti, Daria Capece, Francesca Zazzeroni, Vasiliki Liakouli, Ilenia Pantano, Onorina Berardicurti, Francesco Carubbi, Gianluca Pecetti, Stefano Turricchia, Edoardo Alesse, Marc Iglarz, Roberto Giacomelli
The Journal of Rheumatology Aug 2015, jrheum.150088; DOI: 10.3899/jrheum.150088
The Endothelial-mesenchymal Transition in Systemic Sclerosis Is Induced by Endothelin-1 and Transforming Growth Factor-β and May Be Blocked by Macitentan, a Dual Endothelin-1 Receptor Antagonist
Paola Cipriani, Paola Di Benedetto, Piero Ruscitti, Daria Capece, Francesca Zazzeroni, Vasiliki Liakouli, Ilenia Pantano, Onorina Berardicurti, Francesco Carubbi, Gianluca Pecetti, Stefano Turricchia, Edoardo Alesse, Marc Iglarz, Roberto Giacomelli
The Journal of Rheumatology Aug 2015, jrheum.150088; DOI: 10.3899/jrheum.150088