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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

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

Revista

Título: Clinical And Experimental Pharmacology And Physiology

Vol. 46

Páginas: 255-265

ISSN: 0305-1870

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 9 Citações

Scopus - 9 Citações

Classificação Científica

CORDIS: Ciências da Saúde

FOS: Ciências médicas e da saúde

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 11