Neuregulin-1 attenuates right ventricular diastolic stiffness in experimental pulmonary hypertension

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Adao, R (Author) Other; Mendes Ferreira, P (Author) Other; Maia Rocha, C (Author) Other; Santos Ribeiro, D (Author) Other; Rodrigues, PG (Author) Other; Vidal Meireles, A (Author) Other; Monteiro Pinto, C (Author) Other; Pimentel, LD (Author) Other; Falcao Pires, I (Author) Other; De Keulenaer, GW (Author) Other; Leite Moreira, AF (Author) Other; Brás-Silva C (Author) FMUP

Journal

Title: Clinical And Experimental Pharmacology And Physiology

Vol. 46

Pages: 255-265

ISSN: 0305-1870

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 9 Citations

Scientific classification

CORDIS: Health sciences

FOS: Medical and Health sciences

Other information

Authenticus ID: P-00P-WJ6

DOI: 10.1111/1440-1681.13043

Abstract (EN): We have previously shown that treatment with recombinant human neuregulin-1 (rhNRG-1) improves pulmonary arterial hypertension (PAH) in a monocrotaline (MCT)-induced animal model, by decreasing pulmonary arterial remodelling and endothelial dysfunction, as well as by restoring right ventricular (RV) function. Additionally, rhNRG-1 treatment showed direct myocardial anti-remodelling effects in a model of pressure loading of the RV without PAH. This work aimed to study the intrinsic cardiac effects of rhNRG-1 on experimental PAH and RV pressure overload, and more specifically on diastolic stiffness, at both the ventricular and cardiomyocyte level. We studied the effects of chronic rhNRG-1 treatment on ventricular passive stiffness in RV and LV samples from MCT-induced PAH animals and in the RV from animals with compensated and decompensated RV hypertrophy, through a mild and severe pulmonary artery banding (PAB). We also measured passive tension in isolated cardiomyocytes and quantified the expression of myocardial remodelling-associated genes and calcium handling proteins. Chronic rhNRG-1 treatment decreased passive tension development in RV and LV isolated from animals with MCT-induced PAH. This decrease was associated with increased phospholamban phosphorylation, and with attenuation of the expression of cardiac maladaptive remodelling markers. Finally, we showed that rhNRG-1 therapy decreased RV remodelling and cardiomyocyte passive tension development in PAB-induced RV hypertrophy animals, without compromising cardiac function, pointing to cardiac-specific effects in both hypertrophy stages. In conclusion, we demonstrated that rhNRG-1 treatment decreased RV intrinsic diastolic stiffness, through the improvement of calcium handling and cardiac remodelling signalling.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11