Schnelle, Moritz Thomas

[["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","H422"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","American Journal of Physiology-Heart and Circulatory Physiology"],["dc.bibliographiccitation.lastpage","H431"],["dc.bibliographiccitation.volume","319"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Chong, Mei"],["dc.contributor.author","Zoccarato, Anna"],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Sawyer, Greta Jane"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Ludwig, Christian"],["dc.contributor.author","Shah, Ajay M."],["dc.date.accessioned","2021-04-14T08:24:01Z"],["dc.date.available","2021-04-14T08:24:01Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1152/ajpheart.00219.2020"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81138"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1522-1539"],["dc.relation.issn","0363-6135"],["dc.title","In vivo [U- 13 C]glucose labeling to assess heart metabolism in murine models of pressure and volume overload"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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.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.artnumber","45"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Cardiovascular Magnetic Resonance"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Lange, Torben"],["dc.contributor.author","Backhaus, Sören J."],["dc.contributor.author","Beuthner, Bo E."],["dc.contributor.author","Topci, Rodi"],["dc.contributor.author","Rigorth, Karl-Rudolf"],["dc.contributor.author","Kowallick, Johannes T."],["dc.contributor.author","Evertz, Ruben"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Ravassa, Susana"],["dc.contributor.author","Díez, Javier"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Seidler, Tim"],["dc.contributor.author","Puls, Miriam"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Schuster, Andreas"],["dc.date.accessioned","2022-08-18T12:40:06Z"],["dc.date.available","2022-08-18T12:40:06Z"],["dc.date.issued","2022-07-28"],["dc.date.updated","2022-07-29T12:18:01Z"],["dc.description.abstract","Abstract\n \n Background\n Since cardiovascular magnetic resonance (CMR) imaging allows comprehensive quantification of both myocardial function and structure we aimed to assess myocardial remodeling processes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR).\n \n \n Methods\n CMR imaging was performed in 40 patients with severe AS before and 1 year after TAVR. Image analyses comprised assessments of myocardial volumes, CMR-feature-tracking based atrial and ventricular strain, myocardial T1 mapping, extracellular volume fraction-based calculation of left ventricular (LV) cellular and matrix volumes, as well as ischemic and non-ischemic late gadolinium enhancement analyses. Moreover, biomarkers including NT-proBNP as well as functional and clinical status were documented.\n \n \n Results\n Myocardial function improved 1 year after TAVR: LV ejection fraction (57.9 ± 16.9% to 65.4 ± 14.5%, p = 0.002); LV global longitudinal (− 21.4 ± 8.0% to -25.0 ± 6.4%, p < 0.001) and circumferential strain (− 36.9 ± 14.3% to − 42.6 ± 11.8%, p = 0.001); left atrial reservoir (13.3 ± 6.3% to 17.8 ± 6.7%, p = 0.001), conduit (5.5 ± 3.2% to 8.4 ± 4.6%, p = 0.001) and boosterpump strain (8.2 ± 4.6% to 9.9 ± 4.2%, p = 0.027). This was paralleled by regression of total myocardial volume (90.3 ± 21.0 ml/m2 to 73.5 ± 17.0 ml/m2, p < 0.001) including cellular (55.2 ± 13.2 ml/m2 to 45.3 ± 11.1 ml/m2, p < 0.001) and matrix volumes (20.7 ± 6.1 ml/m2 to 18.8 ± 5.3 ml/m2, p = 0.036). These changes were paralleled by recovery from heart failure (decrease of NYHA class: p < 0.001; declining NT-proBNP levels: 2456 ± 3002 ng/L to 988 ± 1222 ng/L, p = 0.001).\n \n \n Conclusion\n CMR imaging enables comprehensive detection of myocardial remodeling in patients undergoing TAVR. Regression of LV matrix volume as a surrogate for reversible diffuse myocardial fibrosis is accompanied by increase of myocardial function and recovery from heart failure. Further data are required to define the value of these parameters as therapeutic targets for optimized management of TAVR patients.\n Trial registration DRKS, DRKS00024479. Registered 10 December 2021—Retrospectively registered, \n https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00024479"],["dc.identifier.citation","Journal of Cardiovascular Magnetic Resonance. 2022 Jul 28;24(1):45"],["dc.identifier.doi","10.1186/s12968-022-00874-0"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112977"],["dc.language.iso","en"],["dc.publisher","BioMed Central"],["dc.rights.holder","The Author(s)"],["dc.subject","Cardiac magnetic resonance imaging"],["dc.subject","Transcatheter aortic valve replacement"],["dc.subject","Myocardial remodeling"],["dc.subject","Assessment of myocardial function and structure"],["dc.title","Functional and structural reverse myocardial remodeling following transcatheter aortic valve replacement: a prospective cardiovascular magnetic resonance study"],["dc.type","journal_article"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","20"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","28"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Catibog, Norman"],["dc.contributor.author","Zhang, Min"],["dc.contributor.author","Nabeebaccus, Adam A."],["dc.contributor.author","Anderson, Grace"],["dc.contributor.author","Richards, Daniel A."],["dc.contributor.author","Sawyer, Greta"],["dc.contributor.author","Zhang, Xiaohong"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Monaghan, Mark J."],["dc.contributor.author","Shah, Ajay M."],["dc.date.accessioned","2018-04-23T11:48:04Z"],["dc.date.available","2018-04-23T11:48:04Z"],["dc.date.issued","2018"],["dc.description.abstract","Background Mouse models of heart disease are extensively employed. The echocardiographic characterization of contractile function is usually focused on systolic function with fewer studies assessing diastolic function. Furthermore, the applicability of diverse echocardiographic parameters of diastolic function that are commonly used in humans has not been extensively evaluated in different pathophysiological models in mice. Methods and results We used high resolution echocardiography to evaluate parameters of diastolic function in mouse models of chronic pressure overload (aortic constriction), volume overload (aorto-caval shunt), heart failure with preserved ejection fraction (HFpEF; DOCA-salt hypertension), and acute sarcoplasmic reticulum dysfunction induced by thapsigargin - all known to exhibit diastolic dysfunction. Left atrial area increased in all three chronic models while mitral E/A was difficult to quantify at high heart rates. Isovolumic relaxation time (IVRT) and Doppler E/E′ increased significantly and the peak longitudinal strain rate during early filling (peak reverse longitudinal strain rate) decreased significantly after aortic constriction, with the changes being proportional to the magnitude of hypertrophy. In the HFpEF model, reverse longitudinal strain rate decreased significantly but changes in IVRT and E/E′ were non-significant, consistent with less severe dysfunction. With volume overload, there was a significant increase in reverse longitudinal strain rate and decrease in IVRT, indicating a restrictive physiology. Acute thapsigargin treatment caused significant prolongation of IVRT and decrease in reverse longitudinal strain rate. Conclusion These results indicate that the combined measurement of left atrial area plus reverse longitudinal strain rate and/or IVRT provide an excellent overall assessment of diastolic function in the diseased mouse heart, allowing distinction between different types of pathophysiology."],["dc.identifier.doi","10.1016/j.yjmcc.2017.10.006"],["dc.identifier.gro","3142326"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13460"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0022-2828"],["dc.title","Echocardiographic evaluation of diastolic function in mouse models of heart disease"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2796"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Eidizadeh, Abass"],["dc.contributor.author","Fuhlrott, Katharina"],["dc.contributor.author","Trippel, Tobias D."],["dc.contributor.author","Hashemi, Djawid"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Wachter, Rolf"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Edelmann, Frank"],["dc.contributor.author","Pieske, Burkert"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.editor","Santulli, Gaetano"],["dc.date.accessioned","2021-12-01T09:22:48Z"],["dc.date.available","2021-12-01T09:22:48Z"],["dc.date.issued","2021"],["dc.description.abstract","The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is poorly understood and therapeutic strategies are lacking. This study aimed to identify plasma proteins with pathophysiological relevance in HFpEF and with respect to spironolactone-induced effects. We assessed 92 biomarkers in plasma samples from 386 HFpEF patients—belonging to the Aldo-DHF trial—before (baseline, BL) and after one-year treatment (follow up, FU) with spironolactone (verum) or a placebo. At BL, various biomarkers showed significant associations with the two Aldo-DHF primary end point parameters: 33 with E/e’ and 20 with peak VO2. Ten proteins including adrenomedullin, FGF23 and inflammatory peptides (e.g., TNFRSF11A, TRAILR2) were significantly associated with both parameters, suggesting a role in the clinical HFpEF presentation. For 13 proteins, expression changes from BL to FU were significantly different between verum and placebo. Among them were renin, growth hormone, adrenomedullin and inflammatory proteins (e.g., TNFRSF11A, IL18 and IL4RA), indicating distinct spironolactone-mediated effects. BL levels of five proteins, e.g., inflammatory markers such as CCL17, IL4RA and IL1ra, showed significantly different effects on the instantaneous risk for hospitalization between verum and placebo. This study identified plasma proteins with different implications in HFpEF and following spironolactone treatment. Future studies need to define their precise mechanistic involvement."],["dc.description.abstract","The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is poorly understood and therapeutic strategies are lacking. This study aimed to identify plasma proteins with pathophysiological relevance in HFpEF and with respect to spironolactone-induced effects. We assessed 92 biomarkers in plasma samples from 386 HFpEF patients—belonging to the Aldo-DHF trial—before (baseline, BL) and after one-year treatment (follow up, FU) with spironolactone (verum) or a placebo. At BL, various biomarkers showed significant associations with the two Aldo-DHF primary end point parameters: 33 with E/e’ and 20 with peak VO2. Ten proteins including adrenomedullin, FGF23 and inflammatory peptides (e.g., TNFRSF11A, TRAILR2) were significantly associated with both parameters, suggesting a role in the clinical HFpEF presentation. For 13 proteins, expression changes from BL to FU were significantly different between verum and placebo. Among them were renin, growth hormone, adrenomedullin and inflammatory proteins (e.g., TNFRSF11A, IL18 and IL4RA), indicating distinct spironolactone-mediated effects. BL levels of five proteins, e.g., inflammatory markers such as CCL17, IL4RA and IL1ra, showed significantly different effects on the instantaneous risk for hospitalization between verum and placebo. This study identified plasma proteins with different implications in HFpEF and following spironolactone treatment. Future studies need to define their precise mechanistic involvement."],["dc.identifier.doi","10.3390/cells10102796"],["dc.identifier.pii","cells10102796"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94485"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)."],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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","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.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"]]