Cyganek, Lukas

[["dc.bibliographiccitation.artnumber","2935"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Yücel, Gökhan"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Buljubasic, Fanis"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Utikal, Jochen"],["dc.contributor.author","Ravens, Ursula"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Zhou, Xiao-Bo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2018-04-23T11:49:22Z"],["dc.date.available","2018-04-23T11:49:22Z"],["dc.date.issued","2017"],["dc.description.abstract","Severe infections like sepsis lead frequently to cardiomyopathy. The mechanisms are unclear and an optimal therapy for septic cardiomyopathy still lacks. The aim of this study is to establish an endotoxin-induced inflammatory model using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) for mechanistic and therapeutic studies. hiPSC-CMs were treated by lipopolysaccharide (LPS) in different concentrations for different times. ELISA, FACS, qPCR, and patch-clamp techniques were used for the study. TLR4 (Toll-like receptor 4) and its associated proteins, CD14, LBP (lipopolysaccharide binding protein), TIRAP (toll-interleukin 1 receptor domain containing adaptor protein), Ly96 (lymphocyte antigen 96) and nuclear factor kappa B as well as some pro-and anti-inflammatory factors are expressed in hiPSC-CMs. LPS-treatment for 6 hours increased the expression levels of pro-inflammatory and chemotactic cytokines (TNF-a, IL-1ß, IL-6, CCL2, CCL5, IL-8), whereas 48 hour-treatment elevated the expression of anti-inflammatory factors (IL-10 and IL-6). LPS led to cell injury resulting from exaggerated cell apoptosis and necrosis. Finally, LPS inhibited small conductance Ca2+-activated K+ channel currents, enhanced Na+/Ca2+-exchanger currents, prolonged action potential duration, suggesting cellular electrical dysfunctions. Our data demonstrate that hiPSC-CMs possess the functional reaction system involved in endotoxin-induced inflammation and can model some bacterium-induced inflammatory responses in cardiac myocytes."],["dc.identifier.doi","10.1038/s41598-017-03147-4"],["dc.identifier.gro","3142526"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14783"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13682"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","14689"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Sattler, Katherine"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","Utikal, Jochen"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2021-09-01T06:42:20Z"],["dc.date.available","2021-09-01T06:42:20Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract The non-selective cation channel transient receptor potential vanilloid 1 (TRPV1) is expressed throughout the cardiovascular system. Recent evidence shows a role for TRPV1 in inflammatory processes. The role of TRPV1 for myocardial inflammation has not been established yet. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (hiPSC-CM) from 4 healthy donors were incubated with lipopolysaccharides (LPS, 6 h), TRPV1 agonist capsaicin (CAP, 20 min) or the antagonist capsazepine (CPZ, 20 min). TRPV1 expression was studied by PCR and western blotting. TRPV1 internalization was analyzed by immunofluorescence. Interleukin-6 (IL-6) secretion and phosphorylation of JNK, p38 and ERK were determined by ELISA. TRPV1-associated ion channel current was measured by patch clamp. TRPV1-mRNA and -protein were expressed in hiPSC-CM. TRPV1 was localized in the plasma membrane. LPS significantly increased secretion of IL-6 by 2.3-fold, which was prevented by pre-incubation with CPZ. LPS induced TRPV1 internalization. Phosphorylation levels of ERK, p38 or JNK were not altered by TRPV1 stimulation or inhibition. LPS and IL-6 significantly lowered TRPV1-mediated ion channel current. TRPV1 mediates the LPS-induced inflammation in cardiomyocytes, associated with changes of cellular electrophysiology. LPS-induced inflammation results in TRPV1 internalization. Further studies have to examine the underlying pathways and the clinical relevance of these findings."],["dc.identifier.doi","10.1038/s41598-021-93958-3"],["dc.identifier.pii","93958"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89034"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/399"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","2045-2322"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.rights","CC BY 4.0"],["dc.title","TRPV1 activation and internalization is part of the LPS-induced inflammation in human iPSC-derived cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Cell and Developmental Biology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Müller, Jonas"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Zhong, Rujia"],["dc.contributor.author","Zhang, Feng"],["dc.contributor.author","Kleinsorge, Mandy"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Xu, Qiang"],["dc.contributor.author","Huang, Mengying"],["dc.contributor.author","Liao, Zhenxing"],["dc.contributor.author","Moscu-Gregor, Alexander"],["dc.contributor.author","Albers, Sebastian"],["dc.contributor.author","Dinkel, Hendrik"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Diecke, Sebastian"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Utikal, Jochen"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Zhou, Xiaobo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2020-12-10T18:44:21Z"],["dc.date.available","2020-12-10T18:44:21Z"],["dc.date.issued","2019"],["dc.description.abstract","Background Among rare channelopathies BrS patients are at high risk of sudden cardiac death (SCD). SCN5A mutations are found in a quarter of patients. Other rare gene mutations including SCN1B have been implicated to BrS. Studying the human cellular phenotype of BrS associated with rare gene mutation remains lacking. Objectives We sought to study the cellular phenotype of BrS with the SCN1B gene variants using human-induced pluripotent stem cell (hiPSCs)–derived cardiomyocytes (hiPSC-CMs). Methods and Results A BrS patient suffering from recurrent syncope harboring a two variants (c.629T \\u0026gt; C and c.637C \\u0026gt; A) in SCN1B, which encodes the function-modifying sodium channel beta1 subunit, and three independent healthy subjects were recruited and their skin biopsies were used to generate hiPSCs, which were differentiated into cardiomyocytes (hiPSC-CMs) for studying the cellular electrophysiology. A significantly reduced peak and late sodium channel current (INa) and a shift of activation curve to more positive potential as well as a shift of inactivation curve to more negative potential were detected in hiPSC-CMs of the BrS patient, indicating that the SCN1B variants impact the function of sodium channels in cardiomyocytes. The reduced INa led to a reduction of amplitude (APA) and upstroke velocity (Vmax) of action potentials. Ajmaline, a sodium channel blocker, showed a stronger effect on APA and Vmax in BrS cells as compared to cells from healthy donors. Furthermore, carbachol was able to increase arrhythmia events and the beating frequency in BrS. Conclusion Our hiPSC-CMs from a BrS-patient with two variants in SCN1B recapitulated some key phenotypic features of BrS and can provide a platform for studies on BrS with SCN1B variants."],["dc.identifier.doi","10.3389/fcell.2019.00261"],["dc.identifier.eissn","2296-634X"],["dc.identifier.pmid","31737628"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17195"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78416"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2296-634X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Studying Brugada Syndrome With an SCN1B Variants in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","5651"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Sattler, Katherine"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","Schrottenberg, Christoph"],["dc.contributor.author","Yücel, Gökhan"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Utikal, Jochen"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Ravens, Ursula"],["dc.contributor.author","Bieback, Karen"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Zhou, Xiaobo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2019-07-09T11:51:39Z"],["dc.date.available","2019-07-09T11:51:39Z"],["dc.date.issued","2019"],["dc.description.abstract","Acute myocardial infarction (MI) evokes a systemic inflammatory response and locally the degradation of the necrotic tissue, followed by scar formation. The mechanisms for containment of the infarct zone are not studied well. The study aimed to examine the response of healthy cardiomyocytes to serum of patients with myocardial infarction. Human iPSC-cardiomyocytes (iPSC-CM) generated from two healthy donors were incubated with serum of patients with MI with and without ventricular fibrillation (VF) or of healthy controls. Different cell adhesion molecules were studied by flow cytometry and immunostaining. Cellular electrophysiology was studied by patch clamp. The cell adhesion molecules CD54/ICAM-1, CD58/LFA-3 and CD321/JAM-A were expressed on iPSC-CM within the plasma membrane. Incubation with serum of MI patients reduced the levels of expression of CD54/ICAM-1 and CD321/JAM-A by 15-20%. VF serum was less effective than serum of MI patients without VF. MI serum or VF serum did not affect resting potential, action potential duration or maximum depolarization velocity. Myocardial infarction serum exerts anti-inflammatory effects on healthy cardiomyocytes without affecting their electrical activity, thus helping to contain the infarct zone and to protect healthy tissue. Ventricular fibrillation during MI drives healthy cardiomyocytes towards a pro-inflammatory phenotype."],["dc.identifier.doi","10.1038/s41598-019-42079-z"],["dc.identifier.pmid","30948775"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16161"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59980"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/327"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Serum of patients with acute myocardial infarction prevents inflammation in iPSC-cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]