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Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension.
- 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.
- Subjects :
- Animals
Case-Control Studies
Corticotropin-Releasing Hormone metabolism
Disease Models, Animal
Exercise Tolerance drug effects
Heart Ventricles metabolism
Heart Ventricles physiopathology
Humans
Hypertension, Pulmonary metabolism
Hypertension, Pulmonary physiopathology
Hypertrophy, Right Ventricular metabolism
Hypertrophy, Right Ventricular physiopathology
Male
Pulmonary Artery physiopathology
Rats, Wistar
Receptors, Corticotropin-Releasing Hormone metabolism
Signal Transduction drug effects
Urocortins metabolism
Vascular Remodeling drug effects
Vasodilation drug effects
Ventricular Dysfunction, Right metabolism
Ventricular Dysfunction, Right physiopathology
Ventricular Remodeling drug effects
Antihypertensive Agents pharmacology
Arterial Pressure drug effects
Corticotropin-Releasing Hormone pharmacology
Heart Ventricles drug effects
Hypertension, Pulmonary prevention & control
Hypertrophy, Right Ventricular prevention & control
Pulmonary Artery drug effects
Urocortins pharmacology
Ventricular Dysfunction, Right prevention & control
Ventricular Function, Right drug effects
Subjects
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