Schnelle, Moritz Thomas

[["dc.bibliographiccitation.firstpage","178"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","187"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Sawyer, Iain"],["dc.contributor.author","Anilkumar, Narayana"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Richards, Daniel A."],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Zhang, Min"],["dc.contributor.author","Catibog, Norman"],["dc.contributor.author","Sawyer, Greta"],["dc.contributor.author","Mongue-Din, Héloïse"],["dc.contributor.author","Schröder, Katrin"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Shah, Ajay M."],["dc.date.accessioned","2021-04-14T08:30:10Z"],["dc.date.available","2021-04-14T08:30:10Z"],["dc.date.issued","2019"],["dc.description.abstract","Aims\r\n\r\nChronic pressure or volume overload induce concentric vs. eccentric left ventricular (LV) remodelling, respectively. Previous studies suggest that distinct signalling pathways are involved in these responses. NADPH oxidase-4 (Nox4) is a reactive oxygen species-generating enzyme that can limit detrimental cardiac remodelling in response to pressure overload. This study aimed to assess its role in volume overload-induced remodelling.\r\nMethods and results\r\n\r\nWe compared the responses to creation of an aortocaval fistula (Shunt) to induce volume overload in Nox4-null mice (Nox4−/−) vs. wild-type (WT) littermates. Induction of Shunt resulted in a significant increase in cardiac Nox4 mRNA and protein levels in WT mice as compared to Sham controls. Nox4−/− mice developed less eccentric LV remodelling than WT mice (echocardiographic relative wall thickness: 0.30 vs. 0.27, P < 0.05), with less LV hypertrophy at organ level (increase in LV weight/tibia length ratio of 25% vs. 43%, P < 0.01) and cellular level (cardiomyocyte cross-sectional area: 323 µm2 vs. 379 μm2, P < 0.01). LV ejection fraction, foetal gene expression, interstitial fibrosis, myocardial capillary density, and levels of myocyte apoptosis after Shunt were similar in the two genotypes. Myocardial phospho-Akt levels were increased after induction of Shunt in WT mice, whereas levels decreased in Nox4−/− mice (+29% vs. −21%, P < 0.05), associated with a higher level of phosphorylation of the S6 ribosomal protein (S6) and the eIF4E-binding protein 1 (4E-BP1) in WT compared to Nox4−/− mice. We identified that Akt activation in cardiac cells is augmented by Nox4 via a Src kinase-dependent inactivation of protein phosphatase 2A.\r\nConclusion\r\n\r\nEndogenous Nox4 is required for the full development of eccentric cardiac hypertrophy and remodelling during chronic volume overload. Nox4-dependent activation of Akt and its downstream targets S6 and 4E-BP1 may be involved in this effect."],["dc.identifier.doi","10.1093/cvr/cvz331"],["dc.identifier.pmid","31821410"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83130"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/333"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | D04: Bedeutung der Methylierung von RNA (m6A) und des Histons H3 (H3K4) in der Herzinsuffizienz"],["dc.relation.eissn","1755-3245"],["dc.relation.issn","0008-6363"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.title","NADPH oxidase-4 promotes eccentric cardiac hypertrophy in response to volume overload"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]