Riociguat attenuates the changes in left ventricular proteome and microRNA profile after experimental aortic stenosis in mice
| العنوان: | Riociguat attenuates the changes in left ventricular proteome and microRNA profile after experimental aortic stenosis in mice |
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| المؤلفون: | Alexander Benkner, Julia Rüdebusch, Neetika Nath, Elke Hammer, Karina Grube, Stefan Gross, Vishnu M. Dhople, Gertrud Eckstein, Thomas Meitinger, Lars Kaderali, Uwe Völker, Jens Fielitz, Stephan B. Felix |
| المصدر: | British Journal of Pharmacology. 179:4575-4592 |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Heart Failure, Male, Pharmacology, Proteome, Ventricular Remodeling, Heart Ventricles, Aortic Valve Stenosis, Mice, Inbred C57BL, Disease Models, Animal, Mice, MicroRNAs, Pyrimidines, Animals, Pyrazoles |
| الوصف: | Development and progression of heart failure involve endothelial and myocardial dysfunction as well as a dysregulation of the NO-sGC-cGMP signalling pathway. Recently, we reported that the sGC stimulator riociguat has beneficial effects on cardiac remodelling and progression of heart failure in response to chronic pressure overload. Here, we examined if these beneficial effects of riociguat were also reflected in alterations of the myocardial proteome and microRNA profiles.Male C57BL/6N mice underwent transverse aortic constriction (TAC) and sham-operated mice served as controls. TAC and sham animals were randomised and treated with either riociguat or vehicle for 5 weeks, starting 3 weeks after surgery, when cardiac hypertrophy was established. Afterwards, we performed mass spectrometric proteome analyses and microRNA sequencing of proteins and RNAs, respectively, isolated from left ventricles (LVs).TAC-induced changes of the LV proteome were significantly reduced by treatment with riociguat. Bioinformatics analyses revealed that riociguat improved TAC-induced cardiovascular disease-related pathways, metabolism and energy production, for example, reversed alterations in the levels of myosin heavy chain 7, cardiac phospholamban and ankyrin repeat domain-containing protein 1. Riociguat also attenuated TAC-induced changes of microRNA levels in the LV.The sGC stimulator riociguat exerted beneficial effects on cardiac structure and function during pressure overload, which was accompanied by a reversal of TAC-induced changes of the cardiac proteome and microRNA profile. Our data support the potential of riociguat as a novel therapeutic agent for heart failure. |
| تدمد: | 1476-5381 0007-1188 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c9035d38b0a0a785c452acda9d9717f https://doi.org/10.1111/bph.15910 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2c9035d38b0a0a785c452acda9d9717f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765381 00071188 |
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