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Urotensin Inhibition with Palosuran Could Be a Promising Alternative in Pulmonary Arterial Hypertension

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Abstract

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.

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Acknowledgments

We are very grateful to Actelion Pharmaceuticals Ltd. (Allschwil, Switzerland) for providing palosuran samples.

Conflict of Interest

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Authors and Affiliations

  1. Department of Rheumatology, School of Medicine, Sahinbey Medical Center, Gaziantep University, Gaziantep, 27310, Turkey

    Ahmet Mesut Onat, Yavuz Pehlivan & Bunyamin Kisacik

  2. Department of Internal Medicine, School of Medicine, Sahinbey Medical Center, Gaziantep University, Gaziantep, 27310, Turkey

    Ibrahim Halil Turkbeyler

  3. Department of Physiology, School of Medicine, Gaziantep University, Gaziantep, 27310, Turkey

    Tuncer Demir & Davut Sinan Kaplan

  4. Department of Pathology, School of Veterinary, Firat University, Elazig, Turkey

    Ali Osman Ceribasi

  5. Department of Biochemistry, School of Medicine, Gaziantep University, Gaziantep, 27310, Turkey

    Mustafa Orkmez & Seyithan Taysi

  6. Department of Pathology, School of Medicine, Gaziantep University, Gaziantep, 27310, Turkey

    Ediz Tutar

  7. Department of Rheumatology, School of Medicine, Sahinbey Medical Center, Kahramanmaras Sutcu Imam University, Kahramanmaras, 46310, Turkey

    Mehmet Sayarlioglu

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  1. Ahmet Mesut Onat
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Correspondence to Yavuz Pehlivan.

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Onat, A.M., Pehlivan, Y., Turkbeyler, I.H. et al. Urotensin Inhibition with Palosuran Could Be a Promising Alternative in Pulmonary Arterial Hypertension. Inflammation 36, 405–412 (2013). https://doi.org/10.1007/s10753-012-9559-x

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  • DOI: https://doi.org/10.1007/s10753-012-9559-x

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