{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T08:30:12Z","timestamp":1772094612273,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,2]],"date-time":"2018-12-02T00:00:00Z","timestamp":1543708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008593","name":"European Respiratory Society","doi-asserted-by":"publisher","award":["LTRF\u20102017 01\u201000063"],"award-info":[{"award-number":["LTRF\u20102017 01\u201000063"]}],"id":[{"id":"10.13039\/100008593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>We have previously shown that treatment with recombinant human neuregulin\u20101 (rh<jats:styled-content style=\"fixed-case\">NRG<\/jats:styled-content>\u20101) improves pulmonary arterial hypertension (<jats:styled-content style=\"fixed-case\">PAH<\/jats:styled-content>) in a monocrotaline (<jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>)\u2010induced animal model, by decreasing pulmonary arterial remodelling and endothelial dysfunction, as well as by restoring right ventricular (<jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>) function. Additionally, rh<jats:styled-content style=\"fixed-case\">NRG<\/jats:styled-content>\u20101 treatment showed direct myocardial anti\u2010remodelling effects in a model of pressure loading of the <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> without <jats:styled-content style=\"fixed-case\">PAH<\/jats:styled-content>. This work aimed to study the intrinsic cardiac effects of rh<jats:styled-content style=\"fixed-case\">NRG<\/jats:styled-content>\u20101 on experimental <jats:styled-content style=\"fixed-case\">PAH<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> pressure overload, and more specifically on diastolic stiffness, at both the ventricular and cardiomyocyte level. We studied the effects of chronic rh<jats:styled-content style=\"fixed-case\">NRG<\/jats:styled-content>\u20101 treatment on ventricular passive stiffness in <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content> samples from <jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">PAH<\/jats:styled-content> animals and in the <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> from animals with compensated and decompensated <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> hypertrophy, through a mild and severe pulmonary artery banding (<jats:styled-content style=\"fixed-case\">PAB<\/jats:styled-content>). We also measured passive tension in isolated cardiomyocytes and quantified the expression of myocardial remodelling\u2010associated genes and calcium handling proteins. Chronic rh<jats:styled-content style=\"fixed-case\">NRG<\/jats:styled-content>\u20101 treatment decreased passive tension development in <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content> isolated from animals with <jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">PAH<\/jats:styled-content>. This decrease was associated with increased phospholamban phosphorylation, and with attenuation of the expression of cardiac maladaptive remodelling markers. Finally, we showed that rh<jats:styled-content style=\"fixed-case\">NRG<\/jats:styled-content>\u20101 therapy decreased <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> remodelling and cardiomyocyte passive tension development in <jats:styled-content style=\"fixed-case\">PAB<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> hypertrophy animals, without compromising cardiac function, pointing to cardiac\u2010specific effects in both hypertrophy stages. In conclusion, we demonstrated that rh<jats:styled-content style=\"fixed-case\">NRG<\/jats:styled-content>\u20101 treatment decreased <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content> intrinsic diastolic stiffness, through the improvement of calcium handling and cardiac remodelling signalling.<\/jats:p>","DOI":"10.1111\/1440-1681.13043","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T15:09:44Z","timestamp":1539961784000},"page":"255-265","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Neuregulin\u20101 attenuates right ventricular diastolic stiffness in experimental pulmonary hypertension"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2203-436X","authenticated-orcid":false,"given":"Rui","family":"Ad\u00e3o","sequence":"first","affiliation":[{"name":"Department of Surgery and Physiology UnIC\u2014Cardiovascular Research 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