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

Authors :
Adão R
Mendes-Ferreira P
Santos-Ribeiro D
Maia-Rocha C
Pimentel LD
Monteiro-Pinto C
Mulvaney EP
Reid HM
Kinsella BT
Potus F
Breuils-Bonnet S
Rademaker MT
Provencher S
Bonnet S
Leite-Moreira AF
Brás-Silva C
Source :
Cardiovascular research [Cardiovasc Res] 2018 Jul 01; Vol. 114 (8), pp. 1165-1177.
Publication Year :
2018

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).<br />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.<br />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.

Details

Language :
English
ISSN :
1755-3245
Volume :
114
Issue :
8
Database :
MEDLINE
Journal :
Cardiovascular research
Publication Type :
Academic Journal
Accession number :
29584808
Full Text :
https://doi.org/10.1093/cvr/cvy076