Sossalla, Samuel Tobias

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Stehle, Thea"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Knierim, Maria"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Holzamer, Andreas"],["dc.contributor.author","Hilker, Michael"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2020-12-10T14:10:25Z"],["dc.date.available","2020-12-10T14:10:25Z"],["dc.date.issued","2020"],["dc.description.abstract","Pharmacologic approaches for the treatment of atrial arrhythmias are limited due to side effects and low efficacy. Thus, the identification of new antiarrhythmic targets is of clinical interest. Recent genome studies suggested an involvement of SCN10A sodium channels (NaV1.8) in atrial electrophysiology. This study investigated the role and involvement of NaV1.8 (SCN10A) in arrhythmia generation in the human atria and in mice lacking NaV1.8. NaV1.8 mRNA and protein were detected in human atrial myocardium at a significant higher level compared to ventricular myocardium. Expression of NaV1.8 and NaV1.5 did not differ between myocardium from patients with atrial fibrillation and sinus rhythm. To determine the electrophysiological role of NaV1.8, we investigated isolated human atrial cardiomyocytes from patients with sinus rhythm stimulated with isoproterenol. Inhibition of NaV1.8 by A-803467 or PF-01247324 showed no effects on the human atrial action potential. However, we found that NaV1.8 significantly contributes to late Na+ current and consequently to an increased proarrhythmogenic diastolic sarcoplasmic reticulum Ca2+ leak in human atrial cardiomyocytes. Selective pharmacological inhibition of NaV1.8 potently reduced late Na+ current, proarrhythmic diastolic Ca2+ release, delayed afterdepolarizations as well as spontaneous action potentials. These findings could be confirmed in murine atrial cardiomyocytes from wild-type mice and also compared to SCN10A−/− mice (genetic ablation of NaV1.8). Pharmacological NaV1.8 inhibition showed no effects in SCN10A−/− mice. Importantly, in vivo experiments in SCN10A−/− mice showed that genetic ablation of NaV1.8 protects against atrial fibrillation induction. This study demonstrates that NaV1.8 is expressed in the murine and human atria and contributes to late Na+ current generation and cellular arrhythmogenesis. Blocking NaV1.8 selectively counteracts this pathomechanism and protects against atrial arrhythmias. Thus, our translational study reveals a new selective therapeutic target for treating atrial arrhythmias."],["dc.identifier.doi","10.1007/s00395-020-0780-8"],["dc.identifier.pmid","32078054"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70756"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/349"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.rights","CC BY 4.0"],["dc.title","Inhibition of NaV1.8 prevents atrial arrhythmogenesis in human and mice"],["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","102"],["dc.bibliographiccitation.journal","International Journal of Cardiology"],["dc.bibliographiccitation.lastpage","107"],["dc.bibliographiccitation.volume","272"],["dc.contributor.author","Bergau, Leonard"],["dc.contributor.author","Willems, Rik"],["dc.contributor.author","Sprenkeler, David J."],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Flevari, Panayota"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Katsaras, Dimitrios"],["dc.contributor.author","Kirova, Aleksandra"],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Lüthje, Lars"],["dc.contributor.author","Röver, Christian"],["dc.contributor.author","Seegers, Joachim"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Dunnink, Albert"],["dc.contributor.author","Sritharan, Rajevaa"],["dc.contributor.author","Tuinenburg, Anton E."],["dc.contributor.author","Vandenberk, Bert"],["dc.contributor.author","Vos, Marc A."],["dc.contributor.author","Wijers, Sofieke C."],["dc.contributor.author","Friede, Tim"],["dc.contributor.author","Zabel, Markus"],["dc.date.accessioned","2019-07-09T11:50:23Z"],["dc.date.available","2019-07-09T11:50:23Z"],["dc.date.issued","2018"],["dc.description.abstract","BACKGROUND AND OBJECTIVE: We prospectively investigated combinations of risk stratifiers including multiple EP diagnostics in a cohort study of ICD patients. METHODS: For 672 enrolled patients, we collected history, LVEF, EP study and T-wave alternans testing, 24-h Holter, NT-proBNP, and the eGFR. All-cause mortality and first appropriate ICD shock were predefined endpoints. RESULTS: The 635 patients included in the final analyses were 63 ± 13 years old, 81% were male, LVEF averaged 40 ± 14%, 20% were inducible at EP study, 63% had a primary prophylactic ICD. During follow-up over 4.3 ± 1.5 years, 108 patients died (4.0% per year), and appropriate shock therapy occurred in n = 96 (3.9% per year). In multivariate regression, age (p < 0.001), LVEF (p < 0.001), NYHA functional class (p = 0.007), eGFR (p = 0.024), a history of atrial fibrillation (p = 0.011), and NT-pro-BNP (p = 0.002) were predictors of mortality. LVEF (p = 0.002), inducibility at EP study (p = 0.007), and secondary prophylaxis (p = 0.002) were identified as independent predictors of appropriate shocks. A high annualized risk of shocks of about 10% per year was prevalent in the upper quintile of the shock score. In contrast, a low annual risk of shocks (1.8% per year) was found in the lower two quintiles of the shock score. The lower two quintiles of the mortality score featured an annual mortality <0.6%. CONCLUSIONS: In a prospective ICD patient cohort, a very good approximation of mortality versus arrhythmic risk was possible using a multivariable diagnostic strategy. EP stimulation is the best test to assess risk of arrhythmias resulting in ICD shocks."],["dc.identifier.doi","10.1016/j.ijcard.2018.06.103"],["dc.identifier.pmid","29983251"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15929"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59764"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/15360 but duplicate"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/241526/EU//EUTRIGTREAT"],["dc.relation.issn","1874-1754"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.access","openAccess"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.subject.mesh","Aged"],["dc.subject.mesh","Aged, 80 and over"],["dc.subject.mesh","Arrhythmias, Cardiac"],["dc.subject.mesh","Cohort Studies"],["dc.subject.mesh","Death, Sudden, Cardiac"],["dc.subject.mesh","Defibrillators"],["dc.subject.mesh","Defibrillators, Implantable"],["dc.subject.mesh","Female"],["dc.subject.mesh","Follow-Up Studies"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Male"],["dc.subject.mesh","Middle Aged"],["dc.subject.mesh","Mortality"],["dc.subject.mesh","Multivariate Analysis"],["dc.subject.mesh","Natriuretic Peptide, Brain"],["dc.subject.mesh","Peptide Fragments"],["dc.subject.mesh","Prospective Studies"],["dc.subject.mesh","Risk Factors"],["dc.title","Differential multivariable risk prediction of appropriate shock versus competing mortality - A prospective cohort study to estimate benefits from ICD therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","975"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","991"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Borchert, Thomas"],["dc.contributor.author","Hübscher, Daniela"],["dc.contributor.author","Guessoum, Celina I."],["dc.contributor.author","Lam, Tuan-Dinh D."],["dc.contributor.author","Ghadri, Jelena R."],["dc.contributor.author","Schellinger, Isabel N."],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Liaw, Norman Y."],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Haas, Jan"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Huber, Mia A."],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Raaz, Uwe"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Lüscher, Thomas F."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Templin, Christian"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.date.accessioned","2018-04-23T11:48:11Z"],["dc.date.available","2018-04-23T11:48:11Z"],["dc.date.issued","2017"],["dc.description.abstract","Background Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. Objectives The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS. Methods Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function. Results Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate–dependent protein kinase A–mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β1-adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function. Conclusions Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype."],["dc.identifier.doi","10.1016/j.jacc.2017.06.061"],["dc.identifier.gro","3142333"],["dc.identifier.pmid","28818208"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16489"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13468"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/204"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["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 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation.issn","0735-1097"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.relation.workinggroup","RG Dressel"],["dc.relation.workinggroup","RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Wollnik"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","673"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","680"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Schillinger, Wolfgang"],["dc.contributor.author","Teucher, Nils"],["dc.contributor.author","Christians, Claus"],["dc.contributor.author","Kohlhaas, Michael"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Van Nguyen, Phuc"],["dc.contributor.author","Schmidt, Albrecht G."],["dc.contributor.author","Schunck, Ortwin"],["dc.contributor.author","Nebendahl, Klaus"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Zeitz, Oliver"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.date.accessioned","2017-09-07T11:52:27Z"],["dc.date.available","2017-09-07T11:52:27Z"],["dc.date.issued","2006"],["dc.description.abstract","We investigated the hypothesis that increased intracellular [Na+](i) in heart failure contributes to preservation of SR Ca2+ load which may become particularly evident at slow heart rates. [Na+]i in SBFI-loaded myocytes from rabbits with pacing-induced heart failure (PHF) was significantly higher at each frequency as compared to Sham-operated animals. Furthermore, PHF rabbits demonstrated reduced SR Ca2+-ATPase protein levels (-37%, p < 0.04) but unchanged Na+/Ca2+ exchanger protein levels. At 0.25 Hz, isometric force was similar in cardiac trabeculae from PHF rabbits as compared to control (PHF, 3.6 +/- 1.3; Sham, 4.4 +/- 0.6 mN/mm(2)). Rapid cooling contractures (RCCs) were unchanged indicating preserved SR Ca2+ load at this frequency. In Sham, isometric twitch force increased with rising frequencies to 29.0 +/- 2.8 mN/mm(2) at 3.0 Hz (p < 0.05) as compared to 0.25 Hz. RCCs showed a parallel increase by 186 +/- 47% (p < 0.01). In PHF, frequency-dependent increase in force (15.8 +/- 4.7 mN/mm(2) at 3.0 Hz) and RCCs (increase by 70 +/- 40%) were significantly blunted. Thus, in PHF in rabbits SR Ca2+ load is preserved at low frequencies despite decreased SR Ca2+-ATPase expression. This may result from [Na+](i)-dependent changes in Na+/Ca2+ exchanger activity. (c) 2006 European Society of Cardiology. Published by Elsevier B.V All rights reserved."],["dc.identifier.doi","10.1016/j.ejheart.2006.01.013"],["dc.identifier.gro","3143598"],["dc.identifier.isi","000242383300002"],["dc.identifier.pmid","16540370"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1130"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1388-9842"],["dc.title","High intracellular Na+ preserves myocardial function at low heart rates in isolated myocardium from failing hearts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","32"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","43"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Rasenack, Eva C. L."],["dc.contributor.author","Ruff, Hanna"],["dc.contributor.author","Weber, Sarah L."],["dc.contributor.author","Schoendube, Friedrich A."],["dc.contributor.author","Tirilomis, Theodor"],["dc.contributor.author","Tenderich, Gero"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:48:16Z"],["dc.date.available","2017-09-07T11:48:16Z"],["dc.date.issued","2008"],["dc.description.abstract","The goal of this study was to test the hypothesis that the novel anti-ischemic drug ratiolazine, which is known to inhibit late I-Na, could reduce intracellular [Na+](i) and diastolic [Ca2+](i) overload and improve diastolic function. Contractile dysfunction in human heart failure (HF) is associated with increased [Na+](i) and elevated diastolic [Ca2+](i). Increased Na influx through voltage-gated Na+ channels (late I-Na) has been suggested to contribute to elevated [Na+](i) in HF. In isometrically contracting ventricular muscle strips from end-stage failing human hearts, ranolazine (10 mu mol/L) did not exert negative inotropic effects on twitch force amplitude. However, ranolazine significantly reduced frequency-dependent increase in diastolic tension (i.e., diastolic dysfunction) by similar to 30% without significantly affecting sarcoplasmic reticulum (SR) Ca2+ loading. To investigate the mechanism of action of this beneficial effect of ranolazine on diastolic tension, Anemonia sulcata toxin II (ATX-II, 40 nmol/L) was used to increase intracellular Na+ loading in ventricular rabbit myocytes. ATX-II caused a significant rise in [Na+](i) typically seen in heart failure via increased late I-Na. In parallel, ATX-II significantly increased diastolic [Ca2+](i). In the presence of ranolazine the increases in late I-Na, as well as [Na+](i) and diastolic [Ca2+](i) were significantly blunted at all stimulation rates without significantly decreasing Ca2+ transient amplitudes or SR Ca2+ content. In summary, ranolazine reduced the frequency dependent increase in diastolic tension without having negative inotropic effects on contractility of muscles from end-stage failing human hearts. Moreover, in rabbit myocytes the increases in late I-Na, [Na+](i) and [Ca2+](i) caused by ATX-II, were significantly blunted by ranolazine. These results suggest that ratiolazine may be of therapeutic benefit in conditions of diastolic dysfunction due to elevated [Na+](i) and diastolic [Ca2+](i). (C) 2008 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2008.03.006"],["dc.identifier.gro","3143272"],["dc.identifier.isi","000257543800004"],["dc.identifier.pmid","18439620"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/767"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Ltd- Elsevier Science Ltd"],["dc.relation.eissn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.title","Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts - Role of late sodium current and intracellular ion accumulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","Suppl. 1"],["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Eiringhaus, J."],["dc.contributor.author","Wuensche, C."],["dc.contributor.author","Herting, J."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Fischer, T."],["dc.date.accessioned","2022-05-17T07:52:43Z"],["dc.date.available","2022-05-17T07:52:43Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1093/eurheartj/ehz745.0671"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107986"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/319"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A11: Absolute Arrhythmie bei Vorhofflimmern - ein neuer Mechanismus, der zu einer Störung von Ca2+-Homöostase und elektrischer Stabilität in der Transition zur Herzinsuffizienz führt"],["dc.relation.conference","ESC Congress 2019 together with World Congress of Cardiology"],["dc.relation.eventend","2019-09-04"],["dc.relation.eventlocation","Paris"],["dc.relation.eventstart","2019-08-31"],["dc.relation.issn","0195-668X"],["dc.relation.issn","1522-9645"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.title","P3829 Antiarrhythmic effects of Sacubitrilat (LBQ657) on Ca2+ homeostasis in ventricular cardiomyocytes"],["dc.type","conference_paper"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.volume","87"],["dc.contributor.author","Fluschnik, Nina"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Ort, Katharina R."],["dc.contributor.author","Neef, S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars. S."],["dc.date.accessioned","2018-11-07T08:41:33Z"],["dc.date.available","2018-11-07T08:41:33Z"],["dc.date.issued","2010"],["dc.format.extent","S93"],["dc.identifier.isi","000282114100226"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19494"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","0008-6363"],["dc.title","Beneficial effects of CaMKII inhibition in the human failing heart"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Pabel, Stefanie Corinna"],["dc.contributor.author","Herting, J. Jonas"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel T."],["dc.date.accessioned","2018-11-07T10:10:28Z"],["dc.date.available","2018-11-07T10:10:28Z"],["dc.date.issued","2016"],["dc.format.extent","720"],["dc.identifier.isi","000383869503395"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39863"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","Rome, ITALY"],["dc.relation.issn","1522-9645"],["dc.relation.issn","0195-668X"],["dc.title","Antiarrhythmic effects of dantrolene in human cardiomyocytes from patients with atrial fibrillation or heart failure"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","21"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Fomin, Andrey"],["dc.contributor.author","Luo, Xiaojing"],["dc.contributor.author","Li, Wener"],["dc.contributor.author","Fischer, Claudia"],["dc.contributor.author","Özcelik, Cemil"],["dc.contributor.author","Perrot, Andreas"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Haas, Jan"],["dc.contributor.author","Vidal, Ramon Oliveira"],["dc.contributor.author","Rebs, Sabine"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Linke, Wolfgang A."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.date.accessioned","2018-04-23T11:49:17Z"],["dc.date.available","2018-04-23T11:49:17Z"],["dc.date.issued","2017"],["dc.description.abstract","The ability to generate patient-specific induced pluripotent stem cells (iPSCs) provides a unique opportunity for modeling heart disease in vitro. In this study, we generated iPSCs from a patient with dilated cardiomyopathy (DCM) caused by a missense mutation S635A in RNA-binding motif protein 20 (RBM20) and investigated the functionality and cell biology of cardiomyocytes (CMs) derived from patient-specific iPSCs (RBM20-iPSCs). The RBM20-iPSC-CMs showed abnormal distribution of sarcomeric α-actinin and defective calcium handling compared to control-iPSC-CMs, suggesting disorganized myofilament structure and altered calcium machinery in CMs of the RBM20 patient. Engineered heart muscles (EHMs) from RBM20-iPSC-CMs showed that not only active force generation was impaired in RBM20-EHMs but also passive stress of the tissue was decreased, suggesting a higher visco-elasticity of RBM20-EHMs. Furthermore, we observed a reduced titin (TTN) N2B-isoform expression in RBM20-iPSC-CMs by demonstrating a reduction of exon skipping in the PEVK region of TTN and an inhibition of TTN isoform switch. In contrast, in control-iPSC-CMs both TTN isoforms N2B and N2BA were expressed, indicating that the TTN isoform switch occurs already during early cardiogenesis. Using next generation RNA sequencing, we mapped transcriptome and splicing target profiles of RBM20-iPSC-CMs and identified different cardiac gene networks in response to the analyzed RBM20 mutation in cardiac-specific processes. These findings shed the first light on molecular mechanisms of RBM20-dependent pathological cardiac remodeling leading to DCM. Our data demonstrate that iPSC-CMs coupled with EHMs provide a powerful tool for evaluating disease-relevant functional defects and for a deeper mechanistic understanding of alternative splicing-related cardiac diseases."],["dc.identifier.doi","10.1016/j.yjmcc.2017.09.008"],["dc.identifier.gro","3142517"],["dc.identifier.pmid","28941705"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16493"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13672"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/191"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["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 | 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.issn","0022-2828"],["dc.relation.workinggroup","RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Linke (Kardiovaskuläre Physiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Severe DCM phenotype of patient harboring RBM20 mutation S635A can be modeled by patient-specific induced pluripotent stem cell-derived cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1067"],["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.lastpage","1068"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Mason, F."],["dc.contributor.author","Braun, I."],["dc.contributor.author","Voigt, Niels"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel Tobias"],["dc.date.accessioned","2018-11-07T09:53:36Z"],["dc.date.available","2018-11-07T09:53:36Z"],["dc.date.issued","2015"],["dc.identifier.isi","000361205107171"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36361"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","London, ENGLAND"],["dc.relation.issn","1522-9645"],["dc.relation.issn","0195-668X"],["dc.title","The combined effects of ranolazine and low dose dronedarone on atrial vs. ventricular electrophysiology; a novel therapeutic hope?"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]