Khadjeh, Sara

[["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.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"]]