PMID- 28134077
OWN - NLM
STAT- MEDLINE
DCOM- 20170824
LR  - 20181202
IS  - 0392-856X (Print)
IS  - 0392-856X (Linking)
VI  - 35
IP  - 3
DP  - 2017 May-Jun
TI  - Dual endothelin receptor antagonists contrast the effects induced by endothelin-1 
      on cultured human microvascular endothelial cells.
PG  - 484-493
AB  - 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 beta1 (TGFbeta1, 
      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 (10muM) or macitentan (1muM, 10muM) 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 TGFbeta1 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 TGFbeta1-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.
FAU - Soldano, Stefano
AU  - Soldano S
AD  - Research Laboratory and Academic Division of Clinical Rheumatology, Department of 
      Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, 
      Italy.
FAU - Paolino, Sabrina
AU  - Paolino S
AD  - Research Laboratory and Academic Division of Clinical Rheumatology, Department of 
      Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, 
      Italy.
FAU - Pizzorni, Carmen
AU  - Pizzorni C
AD  - Research Laboratory and Academic Division of Clinical Rheumatology, Department of 
      Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, 
      Italy.
FAU - Trombetta, Amelia Chiara
AU  - Trombetta AC
AD  - Research Laboratory and Academic Division of Clinical Rheumatology, Department of 
      Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, 
      Italy.
FAU - Montagna, Paola
AU  - Montagna P
AD  - Research Laboratory and Academic Division of Clinical Rheumatology, Department of 
      Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, 
      Italy.
FAU - Brizzolara, Renata
AU  - Brizzolara R
AD  - Research Laboratory and Academic Division of Clinical Rheumatology, Department of 
      Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, 
      Italy.
FAU - Corallo, Claudio
AU  - Corallo C
AD  - Department of Medicine, Surgery and Neurosciences, Scleroderma Unit, University 
      of Siena, Italy.
FAU - Giordano, Nicola
AU  - Giordano N
AD  - Department of Medicine, Surgery and Neurosciences, Scleroderma Unit, University 
      of Siena, Italy.
FAU - Sulli, Alberto
AU  - Sulli A
AD  - Research Laboratory and Academic Division of Clinical Rheumatology, Department of 
      Internal Medicine, University of Genova, IRCCS AOU San Martino Hospital, Genoa, 
      Italy.
FAU - Cutolo, Maurizio
AU  - Cutolo M
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20170127
PL  - Italy
TA  - Clin Exp Rheumatol
JT  - Clinical and experimental rheumatology
JID - 8308521
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (EDNRB protein, human)
RN  - 0 (Endothelin A Receptor Antagonists)
RN  - 0 (Endothelin B Receptor Antagonists)
RN  - 0 (Endothelin-1)
RN  - 0 (Pyrimidines)
RN  - 0 (Receptor, Endothelin A)
RN  - 0 (Receptor, Endothelin B)
RN  - 0 (Sulfonamides)
RN  - 0 (Transforming Growth Factor beta1)
RN  - Q326023R30 (Bosentan)
RN  - Z9K9Y9WMVL (macitentan)
SB  - IM
MH  - Bosentan
MH  - Cell Shape/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - Endothelial Cells/*drug effects/metabolism/pathology
MH  - Endothelin A Receptor Antagonists/*pharmacology
MH  - Endothelin B Receptor Antagonists/*pharmacology
MH  - Endothelin-1/*pharmacology
MH  - Epithelial-Mesenchymal Transition/drug effects
MH  - Humans
MH  - Microvessels/*drug effects/metabolism/pathology
MH  - Myofibroblasts/drug effects/metabolism/pathology
MH  - Phenotype
MH  - Pyrimidines/*pharmacology
MH  - Receptor, Endothelin A/*drug effects/metabolism
MH  - Receptor, Endothelin B/*drug effects/metabolism
MH  - Sulfonamides/*pharmacology
MH  - Time Factors
MH  - Transforming Growth Factor beta1/pharmacology
EDAT- 2017/01/31 06:00
MHDA- 2017/08/25 06:00
CRDT- 2017/01/31 06:00
PHST- 2016/08/11 00:00 [received]
PHST- 2016/11/21 00:00 [accepted]
PHST- 2017/01/31 06:00 [pubmed]
PHST- 2017/08/25 06:00 [medline]
PHST- 2017/01/31 06:00 [entrez]
AID - 11022 [pii]
PST - ppublish
SO  - Clin Exp Rheumatol. 2017 May-Jun;35(3):484-493. Epub 2017 Jan 27.