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Author(s): Adao, R
Mendes Ferreira, P
Maia Rocha, C
Santos Ribeiro, D
Rodrigues, PG
Vidal Meireles, A
Monteiro Pinto, C
Pimentel, LD
Falcao Pires, I
De Keulenaer, GW
Leite Moreira, AF
Brás-Silva C
Title: Neuregulin-1 attenuates right ventricular diastolic stiffness in experimental pulmonary hypertension
Issue Date: 2019
Abstract: 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.
Subject: Ciências da Saúde, Ciências médicas e da saúde
Health sciences, Medical and Health sciences
Scientific areas: Ciências médicas e da saúde
Medical and Health sciences
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:FMUP - Artigo em Revista Científica Internacional

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