Zeisberg, Elisabeth M.

[["dc.bibliographiccitation.firstpage","629"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Seminars in nephrology"],["dc.bibliographiccitation.lastpage","636"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Hulshoff, Melanie S."],["dc.contributor.author","Rath, Sandip K."],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.date.accessioned","2020-11-24T12:13:03Z"],["dc.date.available","2020-11-24T12:13:03Z"],["dc.date.issued","2018"],["dc.description.abstract","Cardiovascular disease and heart failure are the primary cause of morbidity and mortality in patients with chronic kidney disease. Because impairment of kidney function correlates with heart failure and cardiac fibrosis, a kidney-heart axis is suspected. Although our understanding of the underlying mechanisms still is evolving, the possibility that kidney-heart messengers could be intercepted offers ample reason to focus on this clinically highly relevant problem. Here, we review the current knowledge of how kidney injury causes heart failure and fibrosis."],["dc.identifier.doi","10.1016/j.semnephrol.2018.08.007"],["dc.identifier.pmid","30413256"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69168"],["dc.language.iso","en"],["dc.relation.eissn","1558-4488"],["dc.relation.issn","0270-9295"],["dc.title","Causal Connections From Chronic Kidney Disease to Cardiac Fibrosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1986"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Arteriosclerosis, Thrombosis, and Vascular Biology"],["dc.bibliographiccitation.lastpage","1996"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Hulshoff, Melanie S."],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Krenning, Guido"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.date.accessioned","2020-12-10T18:37:55Z"],["dc.date.available","2020-12-10T18:37:55Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1161/ATVBAHA.118.311276"],["dc.identifier.eissn","1524-4636"],["dc.identifier.issn","1079-5642"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77137"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Epigenetic Regulation of Endothelial-to-Mesenchymal Transition in Chronic Heart Disease"],["dc.title.alternative","Histone Modifications, DNA Methylation, and Noncoding RNAs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.contributor.author","Michurina, Alexandra"],["dc.contributor.author","Sakib, Sadman"],["dc.contributor.author","Kerimoglu, Cemil"],["dc.contributor.author","Krüger, Dennis Manfred"],["dc.contributor.author","Kaurani, Lalit"],["dc.contributor.author","Islam, Rezaul"],["dc.contributor.author","Centeno, Tonatiuh Pena"],["dc.contributor.author","Cha, Julia"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.author","Kranz, Andrea"],["dc.contributor.author","Stewart, Francis Adrian"],["dc.contributor.author","Fischer, André"],["dc.date.accessioned","2022-02-23T13:16:18Z"],["dc.date.available","2022-02-23T13:16:18Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1101/2020.08.07.240853"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100364"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/165"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)"],["dc.relation.workinggroup","RG E. Zeisberg (Kardiales Stroma)"],["dc.title","SETD1B controls cognitive function via cell type specific regulation of neuronal identity genes"],["dc.type","preprint"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3905"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Theranostics"],["dc.bibliographiccitation.lastpage","3924"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Wilhelmi, Tim"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Hulshoff, Melanie S."],["dc.contributor.author","Maamari, Sabine"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.date.accessioned","2020-11-24T12:15:58Z"],["dc.date.available","2020-11-24T12:15:58Z"],["dc.date.issued","2020"],["dc.description.abstract","Rationale: Cardiac fibrosis is an integral constituent of every form of chronic heart disease, and persistence of fibrosis reduces tissue compliance and accelerates the progression to heart failure. Relaxin-2 is a human hormone, which has various physiological functions such as mediating renal vasodilation in pregnancy. Its recombinant form Serelaxin has recently been tested in clinical trials as a therapy for acute heart failure but did not meet its primary endpoints. The aim of this study is to examine whether Serelaxin has an anti-fibrotic effect in the heart and therefore could be beneficial in chronic heart failure. Methods: We utilized two different cardiac fibrosis mouse models (ascending aortic constriction (AAC) and Angiotensin II (ATII) administration via osmotic minipumps) to assess the anti-fibrotic potential of Serelaxin. Histological analysis, immunofluorescence staining and molecular analysis were performed to assess the fibrosis level and indicate endothelial cells which are undergoing EndMT. In vitro TGFβ1-induced endothelial-to-mesenchymal transition (EndMT) assays were performed in human coronary artery endothelial cells and mouse cardiac endothelial cells (MCECs) and were examined using molecular methods. Chromatin immunoprecipitation-qPCR assay was utilized to identify the Serelaxin effect on chromatin remodeling in the Rxfp1 promoter region in MCECs. Results: Our results demonstrate a significant and dose-dependent anti-fibrotic effect of Serelaxin in the heart in both models. We further show that Serelaxin mediates this effect, at least in part, through inhibition of EndMT through the endothelial Relaxin family peptide receptor 1 (RXFP1). We further demonstrate that Serelaxin administration is able to increase its own receptor expression (RXFP1) through epigenetic regulation in form of histone modifications by attenuating TGFβ-pSMAD2/3 signaling in endothelial cells. Conclusions: This study is the first to identify that Serelaxin increases the expression of its own receptor RXFP1 and that this mediates the inhibition of EndMT and cardiac fibrosis, suggesting that Serelaxin may have a beneficial effect as anti-fibrotic therapy in chronic heart failure."],["dc.identifier.doi","10.7150/thno.38640"],["dc.identifier.pmid","32226528"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69204"],["dc.language.iso","en"],["dc.relation.issn","1838-7640"],["dc.title","Serelaxin alleviates cardiac fibrosis through inhibiting endothelial-to-mesenchymal transition via RXFP1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","857"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","866"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Friehs, Ingeborg"],["dc.contributor.author","Hu, Tachi Zhong"],["dc.contributor.author","Melnychenko, Ivan"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Alnour, Fouzi"],["dc.contributor.author","Iascone, Maria"],["dc.contributor.author","Kalluri, Raghu"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","del Nido, Pedro J."],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.date.accessioned","2018-11-07T10:00:47Z"],["dc.date.available","2018-11-07T10:00:47Z"],["dc.date.issued","2015"],["dc.description.abstract","Rationale: Endocardial fibroelastosis (EFE) is a unique form of fibrosis, which forms a de novo subendocardial tissue layer encapsulating the myocardium and stunting its growth, and which is typically associated with congenital heart diseases of heterogeneous origin, such as hypoplastic left heart syndrome. Relevance of EFE was only recently highlighted through the establishment of staged biventricular repair surgery in infant patients with hypoplastic left heart syndrome, where surgical removal of EFE tissue has resulted in improvement in the restrictive physiology leading to the growth of the left ventricle in parallel with somatic growth. However, pathomechanisms underlying EFE formation are still scarce, and specific therapeutic targets are not yet known. Objective: Here, we aimed to investigate the cellular origins of EFE tissue and to gain insights into the underlying molecular mechanisms to ultimately develop novel therapeutic strategies. Methods and Results: By utilizing a novel EFE model of heterotopic transplantation of hearts from newborn reporter mice and by analyzing human EFE tissue, we demonstrate for the first time that fibrogenic cells within EFE tissue originate from endocardial endothelial cells via aberrant endothelial to mesenchymal transition. We further demonstrate that such aberrant endothelial to mesenchymal transition involving endocardial endothelial cells is caused by dysregulated transforming growth factor beta/bone morphogenetic proteins signaling and that this imbalance is at least in part caused by aberrant promoter methylation and subsequent transcriptional suppression of bone morphogenetic proteins 5 and 7. Finally, we provide evidence that supplementation of exogenous recombinant bone morphogenetic proteins 7 effectively ameliorates endothelial to mesenchymal transition and experimental EFE in rats. Conclusions: In summary, our data point to aberrant endothelial to mesenchymal transition as a common denominator of infant EFE development in heterogeneous, congenital heart diseases, and to bone morphogenetic proteins 7 as an effective treatment for EFE and its restriction of heart growth."],["dc.identifier.doi","10.1161/CIRCRESAHA.116.305629"],["dc.identifier.isi","000350395400016"],["dc.identifier.pmid","25587097"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37883"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/114"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C01: Epigenetische Kontrolle der Herzfibrose"],["dc.relation.issn","1524-4571"],["dc.relation.issn","0009-7330"],["dc.relation.workinggroup","RG E. Zeisberg (Kardiales Stroma)"],["dc.relation.workinggroup","RG M. Zeisberg (Renale Fibrogenese)"],["dc.title","Endocardial Fibroelastosis Is Caused by Aberrant Endothelial to Mesenchymal Transition"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","195"],["dc.bibliographiccitation.lastpage","206"],["dc.bibliographiccitation.seriesnr","2272"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.editor","Bogdanovic, Ozren"],["dc.contributor.editor","Vermeulen, Michiel"],["dc.date.accessioned","2021-06-02T10:44:22Z"],["dc.date.available","2021-06-02T10:44:22Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1007/978-1-0716-1294-1_11"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87014"],["dc.notes.intern","DOI-Import GROB-425"],["dc.publisher","Springer US"],["dc.publisher.place","New York, NY"],["dc.relation.crisseries","Methods in Molecular Biology"],["dc.relation.eisbn","978-1-0716-1294-1"],["dc.relation.isbn","978-1-0716-1293-4"],["dc.relation.ispartof","Methods in Molecular Biology"],["dc.relation.ispartof","TET Proteins and DNA Demethylation : Methods and Protocols"],["dc.relation.ispartofseries","Methods in Molecular Biology; 2272"],["dc.title","High-Fidelity CRISPR/Cas9-Based Gene-Specific"],["dc.type","book_chapter"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","279"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","291"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Tampe, Bjoern"],["dc.contributor.author","Nyamsuren, Gunsmaa"],["dc.contributor.author","Liu, Xiaopeng"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Kalluri, Raghu"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.date.accessioned","2017-09-07T11:44:32Z"],["dc.date.available","2017-09-07T11:44:32Z"],["dc.date.issued","2015"],["dc.description.abstract","Methylation of CpG island promoters is a prototypical epigenetic mechanism to stably control gene expression. The aim of this study was to elucidate the contribution of aberrant promoter DNA methylation in pathological endothelial to mesenchymal transition (EndMT) and subsequent cardiac fibrosis. In human coronary endothelial cells, TGF beta 1 causes aberrant methylation of RASAL1 promoter, increased Ras-GTP activity, and EndMT. In end-stage failing vs. non-failing human myocardium, increased fibrosis was associated with significantly increased RASAL1 promoter methylation, decreased RASAL1 expression, increased Ras-GTP activity, and increased expression of markers of EndMT. In mice with pressure overload due to ascending aortic constriction, BMP7 significantly reduced RASAL1 promoter methylation, increased RASAL1 expression, and decreased EndMT markers as well as decreased cardiac fibrosis. The ten eleven translocation (TET) family enzyme TET3, which demethylates through hydroxymethylation, was significantly decreased in fibrotic mouse hearts, restored with BMP7, and BMP7 effects were absent in coronary endothelial cells with siRNA knockdown of TET3. Our study provides proof-in-principle evidence that transcriptional suppression of RASAL1 through aberrant promoter methylation contributes to EndMT and ultimately to progression of cardiac fibrosis. Such aberrant methylation can be reversed through Tet3-mediated hydroxymethylation, which can be specifically induced by BMP7. This may reflect a new treatment strategy to stop cardiac fibrosis."],["dc.identifier.doi","10.1093/cvr/cvv015"],["dc.identifier.gro","3141947"],["dc.identifier.isi","000351013000007"],["dc.identifier.pmid","25616414"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2846"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/115"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C01: Epigenetische Kontrolle der Herzfibrose"],["dc.relation.eissn","1755-3245"],["dc.relation.issn","0008-6363"],["dc.relation.workinggroup","RG E. Zeisberg (Kardiales Stroma)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG M. Zeisberg (Renale Fibrogenese)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.title","Epigenetic balance of aberrant Rasal1 promoter methylation and hydroxymethylation regulates cardiac fibrosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]