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Urotensin Inhibition with Palosuran Could Be a Promising Alternative in Pulmonary Arterial Hypertension.
MedLine Citation:
PMID:  23100033     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Pulmonary arterial hypertension (PAH) is a progressive and a life-threatening disease with its high morbidity and mortality ratios. On searching for new shining targets in pathogenesis, we noticed, in our previous studies, urotensin-II (UII) in systemic sclerosis with potent angiogenic and pro-fibrotic features. Owing to the mimicking properties of UII with endothelin-1 (ET1), we attempted to investigate the effect of palosuran in a PAH rat model. Thirty rats were randomly divided into three groups, with each group comprising 10 rats: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran group) received subcutaneous MCT and palosuran. Serum UII, ET1, transforming growth factor-β1 (TGF-β1) levels, pulmonary arteriolar pathology of different diameter vessels, and cardiac indices were evaluated. The ET1, TGF-β1, and UII levels were significantly diminished in the treatment group, similar to the controls (p < 0.001). Right ventricular hypertrophy index and mean pulmonary arterial pressure scores were also significantly reduced in the treatment group (p = 0.001). Finally, in the 50-125-μm diameter arterioles, in contrast to Groups 3 and 1, there was a statistically significant thickness (p < 0.01) in the arteriolar walls of rats in Group 2. The treatment effect on arteries of more than 125-μm diameters was found to be valuable but not significant. Owing to its healing effect on hemodynamic, histological, and biochemical parameters of MCT-induced PAH, palosuran as an antagonist of UII might be an optional treatment alternative for PAH.
Authors:
Ahmet Mesut Onat; Yavuz Pehlivan; Ibrahim Halil Turkbeyler; Tuncer Demir; Davut Sinan Kaplan; Ali Osman Ceribasi; Mustafa Orkmez; Ediz Tutar; Seyithan Taysi; Mehmet Sayarlioglu; Bunyamin Kisacik
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-26
Journal Detail:
Title:  Inflammation     Volume:  -     ISSN:  1573-2576     ISO Abbreviation:  Inflammation     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600105     Medline TA:  Inflammation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Rheumatology, School of Medicine, Sahinbey Medical Center, Gaziantep University, Gaziantep, 27310, Turkey.
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