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Title: Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension

Abstract

Abstract Aims Pulmonary arterial hypertension (PAH) is a devastating disease and treatment options are limited. Urocortin-2 (Ucn-2) has shown promising therapeutic effects in experimental and clinical left ventricular heart failure (HF). Our aim was to analyse the expression of Ucn-2 in human and experimental PAH, and to investigate the effects of human Ucn-2 (hUcn-2) administration in rats with monocrotaline (MCT)-induced pulmonary hypertension (PH). Methods and results Tissue samples were collected from patients with and without PAH and from rats with MCT-induced PH. hUcn-2 (5 μg/kg, bi-daily, i.p., for 10 days) or vehicle was administered to male wistar rats subjected to MCT injection or to pulmonary artery banding (PAB) to induce right ventricular (RV) overload without PAH. Expression of Ucn-2 and its receptor was increased in the RV of patients and rats with PAH. hUcn-2 treatment reduced PAH in MCT rats, resulting in decreased morbidity, improved exercise capacity and attenuated pulmonary arterial and RV remodelling and dysfunction. Additionally, RV gene expression of hypertrophy and failure signalling pathways were attenuated. hUcn-2 treatment also attenuated PAB-induced RV hypertrophy. Conclusions Ucn-2 levels are altered in human and experimental PAH. hUcn-2 treatment attenuates PAH and RV dysfunction in MCT-induced PH, has direct anti-remodelling effects onmore » the pressure-overloaded RV, and improves pulmonary vascular function.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [2];  [2];  [2];  [3];  [3];  [4];  [3];  [3];  [1];  [5]
  1. Department of Surgery and Physiology, Cardiovascular Research and Development Center - UnIC, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
  2. UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin,Ireland
  3. Pulmonary Hypertension Research Group, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Canada
  4. Department of Medicine, Christchurch Heart Institute, University of Otago-Christchurch, Christchurch, New Zealand
  5. Department of Surgery and Physiology, Cardiovascular Research and Development Center - UnIC, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal, Faculty of Nutrition and Food Sciences, University of Porto, 4200-319 Porto, Portugal
Publication Date:
Sponsoring Org.:
USDOE Office of Nuclear Energy (NE), Fuel Cycle Technologies (NE-5)
OSTI Identifier:
1456292
Grant/Contract Number:  
UID/IC/00051/2013; COMPETE_2020; FCOMP-01-0124-FEDER-028695; SFRH/BD/87714/2012; SFRH/BD/96403/2013
Resource Type:
Published Article
Journal Name:
Cardiovascular Research
Additional Journal Information:
Journal Name: Cardiovascular Research Journal Volume: 114 Journal Issue: 8; Journal ID: ISSN 0008-6363
Publisher:
Oxford University Press
Country of Publication:
United Kingdom
Language:
English

Citation Formats

Adão, Rui, Mendes-Ferreira, Pedro, Santos-Ribeiro, Diana, Maia-Rocha, Carolina, Pimentel, Luís D., Monteiro-Pinto, Cláudia, Mulvaney, Eamon P., Reid, Helen M., Kinsella, B. Therese, Potus, François, Breuils-Bonnet, Sandra, Rademaker, Miriam T., Provencher, Steeve, Bonnet, Sébastien, Leite-Moreira, Adelino F., and Brás-Silva, Carmen. Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension. United Kingdom: N. p., 2018. Web. doi:10.1093/cvr/cvy076.
Adão, Rui, Mendes-Ferreira, Pedro, Santos-Ribeiro, Diana, Maia-Rocha, Carolina, Pimentel, Luís D., Monteiro-Pinto, Cláudia, Mulvaney, Eamon P., Reid, Helen M., Kinsella, B. Therese, Potus, François, Breuils-Bonnet, Sandra, Rademaker, Miriam T., Provencher, Steeve, Bonnet, Sébastien, Leite-Moreira, Adelino F., & Brás-Silva, Carmen. Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension. United Kingdom. doi:10.1093/cvr/cvy076.
Adão, Rui, Mendes-Ferreira, Pedro, Santos-Ribeiro, Diana, Maia-Rocha, Carolina, Pimentel, Luís D., Monteiro-Pinto, Cláudia, Mulvaney, Eamon P., Reid, Helen M., Kinsella, B. Therese, Potus, François, Breuils-Bonnet, Sandra, Rademaker, Miriam T., Provencher, Steeve, Bonnet, Sébastien, Leite-Moreira, Adelino F., and Brás-Silva, Carmen. Fri . "Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension". United Kingdom. doi:10.1093/cvr/cvy076.
@article{osti_1456292,
title = {Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension},
author = {Adão, Rui and Mendes-Ferreira, Pedro and Santos-Ribeiro, Diana and Maia-Rocha, Carolina and Pimentel, Luís D. and Monteiro-Pinto, Cláudia and Mulvaney, Eamon P. and Reid, Helen M. and Kinsella, B. Therese and Potus, François and Breuils-Bonnet, Sandra and Rademaker, Miriam T. and Provencher, Steeve and Bonnet, Sébastien and Leite-Moreira, Adelino F. and Brás-Silva, Carmen},
abstractNote = {Abstract Aims Pulmonary arterial hypertension (PAH) is a devastating disease and treatment options are limited. Urocortin-2 (Ucn-2) has shown promising therapeutic effects in experimental and clinical left ventricular heart failure (HF). Our aim was to analyse the expression of Ucn-2 in human and experimental PAH, and to investigate the effects of human Ucn-2 (hUcn-2) administration in rats with monocrotaline (MCT)-induced pulmonary hypertension (PH). Methods and results Tissue samples were collected from patients with and without PAH and from rats with MCT-induced PH. hUcn-2 (5 μg/kg, bi-daily, i.p., for 10 days) or vehicle was administered to male wistar rats subjected to MCT injection or to pulmonary artery banding (PAB) to induce right ventricular (RV) overload without PAH. Expression of Ucn-2 and its receptor was increased in the RV of patients and rats with PAH. hUcn-2 treatment reduced PAH in MCT rats, resulting in decreased morbidity, improved exercise capacity and attenuated pulmonary arterial and RV remodelling and dysfunction. Additionally, RV gene expression of hypertrophy and failure signalling pathways were attenuated. hUcn-2 treatment also attenuated PAB-induced RV hypertrophy. Conclusions Ucn-2 levels are altered in human and experimental PAH. hUcn-2 treatment attenuates PAH and RV dysfunction in MCT-induced PH, has direct anti-remodelling effects on the pressure-overloaded RV, and improves pulmonary vascular function.},
doi = {10.1093/cvr/cvy076},
journal = {Cardiovascular Research},
number = 8,
volume = 114,
place = {United Kingdom},
year = {2018},
month = {3}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1093/cvr/cvy076

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Cited by: 2 works
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