Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10216/121393
Autor(es): | 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 |
Título: | Neuregulin-1 attenuates right ventricular diastolic stiffness in experimental pulmonary hypertension |
Data de publicação: | 2019 |
Resumo: | 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. |
Assunto: | Ciências da Saúde, Ciências médicas e da saúde Health sciences, Medical and Health sciences |
Áreas do conhecimento: | Ciências médicas e da saúde Medical and Health sciences |
URI: | https://hdl.handle.net/10216/121393 |
Tipo de Documento: | Artigo em Revista Científica Internacional |
Condições de Acesso: | restrictedAccess |
Aparece nas coleções: | FMUP - Artigo em Revista Científica Internacional |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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343920.pdf Restricted Access | 2.03 MB | Adobe PDF | Request a copy from the Author(s) |
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