Mohamed, Belal A.

[["dc.bibliographiccitation.artnumber","149"],["dc.bibliographiccitation.journal","Journal of Translational Medicine"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Qasim, Mohamed"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Lbik, Dawid"],["dc.contributor.author","Schott, Peter"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Toischer, Karl"],["dc.date.accessioned","2017-09-07T11:44:53Z"],["dc.date.available","2017-09-07T11:44:53Z"],["dc.date.issued","2016"],["dc.description.abstract","Background: Hemodynamic load leads to cardiac hypertrophy and heart failure. While afterload (pressure overload) induces concentric hypertrophy, elevation of preload (volume overload) yields eccentric hypertrophy and is associated with a better outcome. Here we analysed the proteomic pattern of mice subjected to short-term preload. Methods and Results: Female FVB/N mice were subjected to aortocaval shunt-induced volume overload that leads to an eccentric hypertrophy (left ventricular weight/tibia length +31 %) with sustained systolic heart function at 1 week after operation. Two-dimensional gel electrophoresis (2-DE) followed by mass spectrometric analysis showed alteration in the expression of 25 protein spots representing 21 different proteins. 64 % of these protein spots were up-regulated and 36 % of the protein spots were consistently down-regulated. Interestingly, alpha-1-antitrypsin was down-regulated, indicating higher elastin degradation and possibly contributing to the early dilatation. In addition to contractile and mitochondrial proteins, polymerase I and transcript release factor protein (PTRF) was also up-regulated, possibly contributing to the preload-induced signal transduction. Conclusions: Our findings reveal the proteomic changes of early-stage eccentric myocardial remodeling after volume overload. Induced expression of some of the respiratory chain enzymes suggests a metabolic shift towards an oxidative phosphorylation that might contribute to the favorable remodeling seen in early VO. Down-regulation of alpha-1-antitrypsin might contribute to extracellular matrix remodeling and left ventricular dilatation. We also identified PTRF as a potential signaling regulator of volume overload-induced cardiac hypertrophy."],["dc.identifier.doi","10.1186/s12967-016-0898-5"],["dc.identifier.gro","3141681"],["dc.identifier.isi","000377182700001"],["dc.identifier.pmid","27234427"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13299"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8784"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: German Research Foundation [SFB1002]"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1479-5876"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Proteomic analysis of short-term preload-induced eccentric cardiac hypertrophy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","9889"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Jakubiczka-Smorag, Joanna"],["dc.contributor.author","Buchholz, Eric"],["dc.contributor.author","Koszewa, Sabrina"],["dc.contributor.author","Lbik, Dawid"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Toischer, Karl"],["dc.date.accessioned","2019-08-06T11:25:13Z"],["dc.date.available","2019-08-06T11:25:13Z"],["dc.date.issued","2019"],["dc.description.abstract","Calcium/calmodulin-dependent protein kinase type II delta (CaMKIIδ), the predominant CaMKII isoform expressed in the heart, has been implicated in the progression of myocardial infarction- and pressure overload-induced pathological remodeling. However, the role of CaMKIIδ in volume overload (VO) has not been explored. We have previously reported an activation of CaMKII during transition to HF in long-term VO. Here, we address whether CaMKIIδ is critically involved in the mortality, myocardial remodeling, and heart failure (HF) progression in response to VO. CaMKIIδ knockout (δ-KO) and wild-type (WT) littermates were exposed to aortocaval shunt-induced VO, and the progression of adverse myocardial remodeling was assessed by serial echocardiography, histological and molecular analyses. The mortality rates during 10 weeks of VO were similar in δ-KO and WT mice. Both genotypes displayed comparable eccentric myocardial hypertrophy, altered left ventricle geometry, perturbed systolic and diastolic functions after shunt. Additionally, cardiomyocytes hypertrophy, augmented myocyte apoptosis, and up-regulation of hypertrophic genes were also not significantly different in δ-KO versus WT hearts after shunt. Therefore, CaMKIIδ signaling seems to be dispensable for the progression of VO-induced maladaptive cardiac remodeling. Accordingly, we hypothesize that CaMKIIδ-inhibition as a therapeutic approach might not be helpful in the context of VO-triggered HF."],["dc.identifier.doi","10.1038/s41598-019-46332-3"],["dc.identifier.pmid","31285482"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16358"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62306"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/281"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["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","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","2045-2322"],["dc.relation.issn","2045-2322"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Genetic deletion of calcium/calmodulin-dependent protein kinase type II delta does not mitigate adverse myocardial remodeling in volume-overloaded hearts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Nicolas, Jan-David"],["dc.contributor.author","Khan, Amara"],["dc.contributor.author","Markus, Andrea"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2021-04-14T08:31:46Z"],["dc.date.available","2021-04-14T08:31:46Z"],["dc.date.issued","2020"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.1038/s41598-020-76163-6"],["dc.identifier.pmid","33168890"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17813"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83706"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/102"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2045-2322"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.relation.workinggroup","RG Alves (Translationale Molekulare Bildgebung)"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","x-ray scattering"],["dc.subject.gro","biomedical tomography"],["dc.title","X-ray diffraction and second harmonic imaging reveal new insights into structural alterations caused by pressure-overload in murine hearts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","362"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","371"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Lbik, Dawid"],["dc.contributor.author","Herwig, Melissa"],["dc.contributor.author","Linke, Wolfgang A."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Toischer, Karl"],["dc.date.accessioned","2017-09-07T11:54:33Z"],["dc.date.available","2017-09-07T11:54:33Z"],["dc.date.issued","2016"],["dc.description.abstract","AimWe have previously reported that early phase (1week) of experimental volume overload (VO) has an adaptive phenotype while wall stress-matched pressure overload (PO) is maladaptive. Here we investigate the transition from adaptation to heart failure (HF) in long-term VO. Methods and resultsFVB/N wild-type mice were subjected to VO induced by aortocaval shunt, and were followed by serial echocardiography until in vivo left ventricular ejection fraction was below <50% (13535days). Heart failure was evident from increased lung and liver weight and increased mortality compared with sham. Maladaptive remodelling resulted in significantly reduced sarcomeric titin phosphorylation (causing increased sarcomeric stiffness), whereas interstitial fibrosis was not increased. This was paralleled by re-expression of the fetal gene program, activation of calcium/calmodulin-dependent protein kinase II (CaMKII), decreased protein kinase B (Akt) phosphorylation, high oxidative stress, and increased apoptosis. Consistently, development of HF and mortality were significantly aggravated in Akt-deficient mice. ConclusionTransition to HF in VO is associated with decreased Akt and increased CaMKII signalling pathways together with increased oxidative stress and apoptosis. Lack of interstitial fibrosis together with sarcomeric titin hypophosphorylation indicates an increased stiffness at the sarcomeric but not matrix level in VO-induced HF (in contrast to PO). Transition to HF may result from myocyte loss and myocyte dysfunction owing to increased stiffness."],["dc.identifier.doi","10.1002/ejhf.465"],["dc.identifier.gro","3141701"],["dc.identifier.isi","000374308700005"],["dc.identifier.pmid","26694078"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/102"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: German Research Foundation DFG [SFB 1002, IRTG1816]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A08: Translationale und posttranslationale Kontrolle trunkierter Titinproteine in Kardiomyozyten von Patienten mit dilatativer Kardiomyopathie"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.eissn","1879-0844"],["dc.relation.issn","1388-9842"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Linke (Kardiovaskuläre Physiologie)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","Molecular and structural transition mechanisms in long-term volume overload"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Hindmarsh, Vanessa"],["dc.contributor.author","Weber, Frederike"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Vidal, Ramon O."],["dc.contributor.author","Torkieh, Setare"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Lbik, Dawid"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.date.accessioned","2020-12-10T14:10:26Z"],["dc.date.available","2020-12-10T14:10:26Z"],["dc.date.issued","2020"],["dc.description.abstract","Heart failure is a major health problem worldwide with a significant morbidity and mortality rate. Although studied extensively in animal models, data from patients at the compensated disease stage are lacking. We sampled myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure and used transcriptomics to study the transition to failure. Sequencing and comparative analysis of analogous samples of mice with transverse aortic constriction identified 25 candidate genes with similar regulation in response to pressure overload, reflecting highly conserved molecular processes. The gene cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is upregulated in the transition to failure in human and mouse and its function is unknown. Homology to ion channel regulatory toxins suggests a role in Ca2+ cycling. CRISPR/Cas9-mediated loss-of-function leads to dysregulated Ca2+ handling in human-induced pluripotent stem cell-derived cardiomyocytes. The downregulation of prohypertrophic, proapoptotic and Ca2+-signaling pathways upon CRISPLD1-KO and its upregulation in the transition to failure implicates a contribution to adverse remodeling. These findings provide new pathophysiological data on Ca2+ regulation in the transition to failure and novel candidate genes with promising potential for therapeutic interventions."],["dc.identifier.doi","10.1007/s00395-020-0784-4"],["dc.identifier.pmid","32146539"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70757"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/350"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["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.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.title","CRISPLD1: a novel conserved target in the transition to human heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["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"]]

[["dc.bibliographiccitation.firstpage","54"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","66"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Berulava, Tea"],["dc.contributor.author","Buchholz, Eric"],["dc.contributor.author","Elerdashvili, Vakhtang"],["dc.contributor.author","Pena, Tonatiuh"],["dc.contributor.author","Islam, Md Rezaul"],["dc.contributor.author","Lbik, Dawid"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Renner, Andre"],["dc.contributor.author","Lewinski, Dirk"],["dc.contributor.author","Sacherer, Michael"],["dc.contributor.author","Bohnsack, Katherine E."],["dc.contributor.author","Bohnsack, Markus T."],["dc.contributor.author","Jain, Gaurav"],["dc.contributor.author","Capece, Vincenzo"],["dc.contributor.author","Cleve, Nicole"],["dc.contributor.author","Burkhardt, Susanne"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Toischer, Karl"],["dc.date.accessioned","2020-12-10T14:06:19Z"],["dc.date.available","2020-12-10T14:06:19Z"],["dc.date.issued","2019"],["dc.description.abstract","ABSTRACT Aims Deregulation of epigenetic processes and aberrant gene expression are important mechanisms in heart failure. Here we studied the potential relevance of m6A RNA methylation in heart failure development. Methods and results We analysed m6A RNA methylation via next‐generation sequencing. We found that approximately one quarter of the transcripts in the healthy mouse and human heart exhibit m6A RNA methylation. During progression to heart failure we observed that changes in m6A RNA methylation exceed changes in gene expression both in mouse and human. RNAs with altered m6A RNA methylation were mainly linked to metabolic and regulatory pathways, while changes in RNA expression level mainly represented changes in structural plasticity. Mechanistically, we could link m6A RNA methylation to altered RNA translation and protein production. Interestingly, differentially methylated but not differentially expressed RNAs showed differential polysomal occupancy, indicating transcription‐independent modulation of translation. Furthermore, mice with a cardiomyocyte restricted knockout of the RNA demethylase Fto exhibited an impaired cardiac function compared to control mice. Conclusions We could show that m6A landscape is altered in heart hypertrophy and heart failure. m6A RNA methylation changes lead to changes in protein abundance, unconnected to mRNA levels. This uncovers a new transcription‐independent mechanisms of translation regulation. Therefore, our data suggest that modulation of epitranscriptomic processes such as m6A methylation might be an interesting target for therapeutic interventions."],["dc.description.sponsorship","German Center for cardiovascular research (DZHK)"],["dc.description.sponsorship","German Center for Neurodegenerative Diseases (DZNE) http://dx.doi.org/10.13039/501100005224"],["dc.description.sponsorship","BMBF http://dx.doi.org/10.13039/501100002347"],["dc.description.sponsorship","German Research Foundation (DFG"],["dc.identifier.doi","10.1002/ejhf.1672"],["dc.identifier.pmid","31849158"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17076"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69851"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/11"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/334"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["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.workinggroup","RG M. Bohnsack (Molecular Biology)"],["dc.relation.workinggroup","RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)"],["dc.relation.workinggroup","RG Hasenfuß"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","Changes in m6A RNA methylation contribute to heart failure progression by modulating translation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1823"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","ESC Heart Failure"],["dc.bibliographiccitation.lastpage","1831"],["dc.bibliographiccitation.volume","9"],["dc.contributor.affiliation","Hartmann, Nico; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nRobert‐Koch‐Str. 40 Göttingen 37075 Germany"],["dc.contributor.affiliation","Preuß, Lena; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nRobert‐Koch‐Str. 40 Göttingen 37075 Germany"],["dc.contributor.affiliation","Mohamed, Belal A.; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nRobert‐Koch‐Str. 40 Göttingen 37075 Germany"],["dc.contributor.affiliation","Schnelle, Moritz; 2\r\nInstitute for Clinical Chemistry\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Renner, Andre; 3\r\nDepartment of Thoracic, Cardiac and Vascular Surgery (Heart and Diabetes Center)\r\nNorth Rhine Westphalia\r\nBad Oeynhausen Germany"],["dc.contributor.affiliation","Hasenfuß, Gerd; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nRobert‐Koch‐Str. 40 Göttingen 37075 Germany"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Preuß, Lena"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Renner, Andre"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Toischer, Karl"],["dc.date.accessioned","2022-04-01T10:01:17Z"],["dc.date.available","2022-04-01T10:01:17Z"],["dc.date.issued","2022"],["dc.date.updated","2022-06-14T23:19:51Z"],["dc.description.abstract","Abstract Aims Pressure overload (PO) and volume overload (VO) lead to concentric or eccentric hypertrophy. Previously, we could show that activation of signalling cascades differ in in vivo mouse models. Activation of these signal cascades could either be induced by intrinsic load sensing or neuro‐endocrine substances like catecholamines or the renin‐angiotensin‐aldosterone system. Methods and results We therefore analysed the activation of classical cardiac signal pathways [mitogen‐activated protein kinases (MAPKs) (ERK, p38, and JNK) and Akt‐GSK3β] in in vitro of mechanical overload (ejecting heart model, rabbit and human isolated muscle strips). Selective elevation of preload in vitro increased AKT and GSK3β phosphorylation after 15 min in isolated rabbit muscles strips (AKT 49%, GSK3β 26%, P < 0.05) and in mouse ejecting hearts (AKT 51%, GSK49%, P < 0.05), whereas phosphorylation of MAPKs was not influenced by increased preload. Selective elevation of afterload revealed an increase in ERK phosphorylation in the ejecting heart (43%, P < 0.05), but not in AKT, GSK3β, and the other MAPKs. Elevation of preload and afterload in the ejecting heart induced a significant phosphorylation of ERK (95%, P < 0.001) and showed a moderate increased AKT (P = 0.14) and GSK3β (P = 0.21) phosphorylation, which did not reach significance. Preload and afterload elevation in muscles strips from human failing hearts showed neither AKT nor ERK phosphorylation changes. Conclusions Our data show that preload activates the AKT–GSK3β and afterload the ERK pathway in vitro, indicating an intrinsic mechanism independent of endocrine signalling."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1002/ehf2.13877"],["dc.identifier.pmid","35315235"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105640"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/425"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation.eissn","2055-5822"],["dc.relation.issn","2055-5822"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.title","Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","229"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Translational Medicine"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Barakat, Amal Z."],["dc.contributor.author","Held, Torsten"],["dc.contributor.author","Rodrigues, Daniel M."],["dc.contributor.author","Mobarak, Sherok"],["dc.contributor.author","Swarnka, Surabhi"],["dc.contributor.author","Adham, Ibrahim M."],["dc.contributor.author","Mohamed, Belal A."],["dc.date.accessioned","2022-06-01T09:39:42Z"],["dc.date.accessioned","2022-08-12T13:52:22Z"],["dc.date.available","2022-06-01T09:39:42Z"],["dc.date.available","2022-08-12T13:52:22Z"],["dc.date.issued","2022-05-14"],["dc.date.updated","2022-07-29T12:17:34Z"],["dc.description.abstract","Background\r\n Molecular chaperones assist protein folding, facilitate degradation of misfolded polypeptides, and thereby maintain protein homeostasis. Impaired chaperone activity leads to defective protein quality control that is implicated in multiple skeletal muscle diseases. The heat shock protein A4 (HSPA4) acts as a co-chaperone for HSP70. Previously, we showed that Hspa4 deletion causes impaired protein homeostasis in the heart. However, its functional role in skeletal muscle has not been explored.\r\n \r\n \r\n Methods\r\n We performed a comparative phenotypic and biochemical analyses of Hspa4 knockout (KO) mice with wild-type (WT) littermates.\r\n \r\n \r\n Results\r\n HSPA4 is markedly upregulated in regenerating WT muscle in vivo, and in differentiated myoblasts in vitro. Hspa4-KO mice are marked by growth retardation and increased variability in body weight, accompanied by 35% mortality rates during the peri-weaning period. The surviving Hspa4-KO mice experienced progressive skeletal muscle myopathy, characterized by increased number of muscle fibers with centralized nuclei, heterogeneous myofiber size distribution, inflammatory cell infiltrates and upregulation of embryonic and perinatal myosin heavy chain transcripts. Hspa4-KO muscles demonstrated an accumulation of autophagosome-associated proteins including microtubule associated protein1 light chain 3-II (LC3-II) and p62/sequestosome accompanied by increased number of TUNEL-positive nuclei.\r\n \r\n \r\n Conclusions\r\n Our findings underscore the indispensable role of HSPA4 in maintenance of muscle integrity through contribution in skeletal muscle autophagy and apoptosis, which might provide a novel therapeutic strategy for skeletal muscle morbidities."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship"," Deutsche Stiftung für Herzforschung"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.citation","Journal of Translational Medicine. 2022 May 14;20(1):229"],["dc.identifier.doi","10.1186/s12967-022-03418-3"],["dc.identifier.pii","3418"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108540"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112725"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation.eissn","1479-5876"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","HSPs"],["dc.subject","Myopathy"],["dc.subject","Autophagy"],["dc.title","Heat shock protein A4 ablation leads to skeletal muscle myopathy associated with dysregulated autophagy and induced apoptosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4440"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","Journal of Cellular and Molecular Medicine"],["dc.bibliographiccitation.lastpage","4452"],["dc.bibliographiccitation.volume","26"],["dc.contributor.affiliation","Mohamed, Belal A.; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Elkenani, Manar; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Mobarak, Sherok; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Marques Rodrigues, Daniel; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Annamalai, Karthika; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Schnelle, Moritz; 2\r\nDZHK (German Centre for Cardiovascular Research)\r\nGöttingen Germany"],["dc.contributor.affiliation","Bader, Michael; 4\r\nMax‐Delbrück‐Center for Molecular Medicine (MDC)\r\nBerlin‐Buch Germany"],["dc.contributor.affiliation","Hasenfuss, Gerd; 1\r\nDepartment of Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Mobarak, Sherok"],["dc.contributor.author","Marques Rodrigues, Daniel"],["dc.contributor.author","Annamalai, Karthika"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Bader, Michael"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Toischer, Karl"],["dc.date.accessioned","2022-08-12T11:32:54Z"],["dc.date.available","2022-08-12T11:32:54Z"],["dc.date.issued","2022-08"],["dc.date.updated","2022-11-11T13:14:07Z"],["dc.description.abstract","Adrenergic stimulation in the heart activates the protein kinase A (PKA), which phosphorylates key proteins involved in intracellular Ca2+ handling. PKA is held in proximity to its substrates by protein scaffolds, the A kinase anchoring proteins (AKAPs). We have previously identified the transcript of phosphodiesterase 4D interacting protein (Pde4dip; also known as myomegalin), one of the sarcomeric AKAPs, as being differentially expressed following hemodynamic overload, a condition inducing hyperadrenergic state in the heart. Here, we addressed whether PDE4DIP is involved in the adverse cardiac remodelling following hemodynamic stress. Homozygous Pde4dip knockout (KO) mice, generated by CRISPR-Cas9 technology, and wild-type (WT) littermates were exposed to aortocaval shunt (shunt) or transthoracic aortic constriction (TAC) to induce hemodynamic volume overload (VO) or pressure overload (PO), respectively. The mortality, cardiac structure, function and pathological cardiac remodelling were followed up after hemodynamic injuries. The PDE4DIP protein level was markedly downregulated in volume-overloaded- but upregulated in pressure-overloaded-WT hearts. Following shunt or TAC, mortality rates were comparably increased in both genotypes. Twelve weeks after shunt or TAC, Pde4dip-KO animals showed a similar degree of cardiac hypertrophy, dilatation and dysfunction as WT mice. Cardiomyocyte hypertrophy, myocardial fibrosis, reactivation of cardiac stress genes and downregulation of ATPase, Ca2+ transporting, cardiac muscle, slow twitch 2 transcript did not differ between WT and Pde4dip-KO hearts following shunt or TAC. In summary, despite a differential expression of PDE4DIP protein in remodelled WT hearts, Pde4dip deficiency does not modulate adverse cardiac remodelling after hemodynamic VO or PO."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1111/jcmm.17468"],["dc.identifier.pmid","35860864"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112714"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/442"],["dc.language.iso","en"],["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","1582-4934"],["dc.relation.issn","1582-1838"],["dc.relation.issn","1582-4934"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.title","Hemodynamic stress-induced cardiac remodelling is not modulated by ablation of phosphodiesterase 4D interacting protein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]