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

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

doi:10.1093/cvr/cvy076

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

Journal Article · Fri Mar 23 00:00:00 EDT 2018 · Cardiovascular Research

DOI:https://doi.org/10.1093/cvr/cvy076· OSTI ID:1456292

Adão, Rui ^[1]; Mendes-Ferreira, Pedro ^[1]; Santos-Ribeiro, Diana ^[1]; Maia-Rocha, Carolina ^[1]; Pimentel, Luís D. ^[1]; Monteiro-Pinto, Cláudia ^[1]; Mulvaney, Eamon P. ^[2]; Reid, Helen M. ^[2]; Kinsella, B. Therese ^[2]; Potus, François ^[3]; Breuils-Bonnet, Sandra ^[3]; Rademaker, Miriam T. ^[4]; Provencher, Steeve ^[3]; Bonnet, Sébastien ^[3]; Leite-Moreira, Adelino F. ^[1]; Brás-Silva, Carmen ^[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
UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin,Ireland
Pulmonary Hypertension Research Group, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Canada
Department of Medicine, Christchurch Heart Institute, University of Otago-Christchurch, Christchurch, New Zealand
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

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.

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Sponsoring Organization:: USDOE Office of Nuclear Energy (NE), Nuclear Fuel Cycle and Supply Chain

OSTI ID:: 1456292

Journal Information:: Cardiovascular Research, Journal Name: Cardiovascular Research Journal Issue: 8 Vol. 114; ISSN 0008-6363

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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