Pabel, Steffen

[["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","642"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","ESC Heart Failure"],["dc.bibliographiccitation.lastpage","648"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Wagemann, Olivia"],["dc.contributor.author","Lücht, Charlotte M."],["dc.contributor.author","Trum, Maximilian"],["dc.contributor.author","Hammer, Karin P."],["dc.contributor.author","Sag, Can Martin"],["dc.contributor.author","Lebek, Simon"],["dc.contributor.author","Tarnowski, Daniel"],["dc.contributor.author","Reinders, Jörg"],["dc.contributor.author","Perbellini, Filippo"],["dc.contributor.author","Terracciano, Cesare"],["dc.contributor.author","Schmid, Christof"],["dc.contributor.author","Schopka, Simon"],["dc.contributor.author","Hilker, Michael"],["dc.contributor.author","Zausig, York"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Schweda, Frank"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Wagner, Stefan"],["dc.date.accessioned","2020-12-10T14:06:09Z"],["dc.date.available","2020-12-10T14:06:09Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1002/ehf2.12336"],["dc.identifier.issn","2055-5822"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69797"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Empagliflozin reduces Ca/calmodulin-dependent kinase II activity in isolated ventricular cardiomyocytes"],["dc.title.alternative","Empagliflozin reduces CaMKII activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1111"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Europace"],["dc.bibliographiccitation.lastpage","1118"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Stehle, Thea"],["dc.contributor.author","Lebek, Simon"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Keyser, Andreas"],["dc.contributor.author","Rupprecht, Leopold"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Maier, Lars S"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2021-04-14T08:24:15Z"],["dc.date.available","2021-04-14T08:24:15Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1093/europace/euaa079"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81221"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1532-2092"],["dc.relation.issn","1099-5129"],["dc.title","Dantrolene reduces CaMKIIδC-mediated atrial arrhythmias"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","95"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","106"],["dc.bibliographiccitation.volume","94"],["dc.contributor.author","Hartmann, Nico H."],["dc.contributor.author","Mason, Fleur E."],["dc.contributor.author","Braun, Inga"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Voigt, Niels"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Dobrev, Dobromir"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Renner, André"],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2017-09-07T11:44:54Z"],["dc.date.available","2017-09-07T11:44:54Z"],["dc.date.issued","2016"],["dc.description.abstract","Introduction: Pharmacological rhythm control of atrial fibrillation (AF) in patients with structural heart disease is limited. Ranolazine in combination with low dose dronedarone remarkably reduced AF-burden in the phase II HARMONY trial. We thus aimed to investigate the possible mechanisms underlying these results. Methods and results: Patch clamp experiments revealed that ranolazine (5 mu M), low-dose dronedarone (0.3 mu M), and the combination significantly prolonged action potential duration (APD(90)) in atrial myocytes from patients in sinus rhythm (prolongation by 23.5 +/- 0.1%, 31.7 +/- 0.1% and 25.6 +/- 0.1% respectively). Most importantly, in atrial myocytes from patients with AF ranolazine alone, but more the combination with dronedarone, also prolonged the typically abbreviated APD(90) (prolongation by 21.6 +/- 0.1% and 31.9 +/- 0.1% respectively). It was clearly observed that neither ranolazine, dronedarone nor the combination significantly changed the APD or contractility and twitch force in ventricular myocytes or trabeculae from patients with heart failure (HF). Interestingly ranolazine, and more so the combination, but not dronedarone alone, caused hyperpolarization of the resting membrane potential in cardiomyocytes from AF. As measured by confocal microscopy (Fluo-3), ranolazine, dronedarone and the combination significantly suppressed diastolic sarcoplasmic reticulum (SR) Ca2+ leak in myocytes from sinus rhythm (reduction by ranolazine: 89.0 +/- 30.7%, dronedarone: 75.6 +/- 27.4% and combination: 78.0 +/- 272%), in myocytes from AF (reduction by ranolazine: 67.6 +/- 33.7%, dronedarone: 86.5 +/- 31.7% and combination: 81.0 +/- 33.3%), as well as in myocytes from HF (reduction by ranolazine: 64.8 +/- 26.5% and dronedarone: 65.9 +/- 29.3%). Conclusions: Electrophysiological measurements during exposure to ranolazine alone or in combination with low-dose dronedarone showed APD prolongation, cellular hyperpolarization and reduced SR Ca2+ leak in human atrial myocytes. The combined inhibitory effects on various currents, in particular Na+ and K+ currents, may explain the anti-AF effects observed in the HARMONY trial. Therefore, the combination of ranolazine and dronedarone, but also ranolazine alone, may be promising new treatment options for AF, especially in patients with HF, and merit further clinical investigation. (C) 2016 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2016.03.012"],["dc.identifier.gro","3141690"],["dc.identifier.isi","000376839000011"],["dc.identifier.pmid","27056421"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8938"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/146"],["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 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.eissn","1095-8584"],["dc.relation.issn","0022-2828"],["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.relation.workinggroup","RG T. Fischer"],["dc.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.title","The combined effects of ranolazine and dronedarone on human atrial and ventricular electrophysiology"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1690"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","1700"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Bollenberg, Hannah"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Kovács, Árpád"],["dc.contributor.author","Schach, Christian"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Fischer, Thomas"],["dc.contributor.author","Van Linthout, Sophie"],["dc.contributor.author","Tschöpe, Carsten"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hamdani, Nazha"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2019-02-19T13:12:22Z"],["dc.date.available","2019-02-19T13:12:22Z"],["dc.date.issued","2018"],["dc.description.abstract","Aims Empagliflozin, a clinically used oral antidiabetic drug that inhibits the sodium-dependent glucose co-transporter 2, has recently been evaluated for its cardiovascular safety. Surprisingly, empagliflozin reduced mortality and hospitalization for heart failure (HF) compared to placebo. However, the underlying mechanisms remain unclear. Therefore, our study aims to investigate whether empagliflozin may cause direct pleiotropic effects on the myocardium. Methods and results In order to assess possible direct myocardial effects of empagliflozin, we performed contractility experiments with in toto-isolated human systolic end-stage HF ventricular trabeculae. Empagliflozin significantly reduced diastolic tension, whereas systolic force was not changed. These results were confirmed in murine myocardium from diabetic and non-diabetic mice, suggesting independent effects from diabetic conditions. In human HF cardiomyocytes, empagliflozin did not influence calcium transient amplitude or diastolic calcium level. The mechanisms underlying the improved diastolic function were further elucidated by studying myocardial fibres from patients and rats with diastolic HF (HF with preserved ejection fraction, HFpEF). Empagliflozin beneficially reduced myofilament passive stiffness by enhancing phosphorylation levels of myofilament regulatory proteins. Intravenous injection of empagliflozin in anaesthetized HFpEF rats significantly improved diastolic function measured by echocardiography, while systolic contractility was unaffected. Conclusion Empagliflozin causes direct pleiotropic effects on the myocardium by improving diastolic stiffness and hence diastolic function. These effects were independent of diabetic conditions. Since pharmacological therapy of diastolic dysfunction and HF is an unmet need, our results provide a rationale for new translational studies and might also contribute to the understanding of the EMPA-REG OUTCOME trial."],["dc.identifier.doi","10.1002/ejhf.1328"],["dc.identifier.pmid","30328645"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57583"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/239"],["dc.language.iso","en"],["dc.notes.status","final"],["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.issn","1879-0844"],["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.relation.workinggroup","RG T. Fischer"],["dc.title","Empagliflozin directly improves diastolic function in human heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","154"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","ESC Heart Failure"],["dc.bibliographiccitation.lastpage","163"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Molina, Cristina E."],["dc.contributor.author","Tirilomis, Theodoros"],["dc.contributor.author","Kutschka, Ingo"],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2019-02-26T11:03:53Z"],["dc.date.available","2019-02-26T11:03:53Z"],["dc.date.issued","2019"],["dc.description.abstract","Aims In hypertrophy and heart failure, the proarrhythmic persistent Na+ current (INaL) is enhanced. We aimed to investigate the electrophysiological role of neuronal sodium channel NaV1.8 in human hypertrophied myocardium. Methods and results Myocardial tissue of 24 patients suffering from symptomatic severe aortic stenosis and concomitant significant afterload-induced hypertrophy with preserved ejection fraction was used and compared with 12 healthy controls. We performed quantitative real-time PCR and western blot and detected a significant up-regulation of NaV1.8 mRNA (2.34fold) and protein expression (1.96-fold) in human hypertrophied myocardium compared with healthy hearts. Interestingly, NaV1.5 protein expression was significantly reduced in parallel (0.60-fold). Using whole-cell patch-clamp technique, we found that the prominent INaL was significantly reduced after addition of novel NaV1.8-specific blockers either A-803467 (30 nM) or PF-01247324 (1 μM) in human hypertrophic cardiomyocytes. This clearly demonstrates the relevant contribution of NaV1.8 to this proarrhythmic current. We observed a significant action potential duration shortening and performed confocal microscopy, demonstrating a 50% decrease in proarrhythmic diastolic sarcoplasmic reticulum (SR)-Ca2+ leak and SR-Ca2+ spark frequency after exposure to both NaV1.8 inhibitors."],["dc.identifier.doi","10.1002/ehf2.12378"],["dc.identifier.pmid","30378291"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57615"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/242"],["dc.language.iso","en"],["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.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-NC 4.0"],["dc.title","The functional consequences of sodium channel NaV1.8 in human left ventricular hypertrophy"],["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","412"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Heart Rhythm"],["dc.bibliographiccitation.lastpage","419"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Hartmann, Nico H."],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Schatter, Felix"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2017-09-07T11:52:35Z"],["dc.date.available","2017-09-07T11:52:35Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1016/j.hrthm.2016.09.014"],["dc.identifier.gro","3144963"],["dc.identifier.pmid","27650424"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2646"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/300"],["dc.notes.intern","Crossref Import"],["dc.notes.status","public"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A03: Bedeutung CaMKII-abhängiger Mechanismen für die Arrhythmogenese bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.issn","1547-5271"],["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.relation.workinggroup","RG T. Fischer"],["dc.title","Antiarrhythmic effects of dantrolene in human diseased cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1689"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of Molecular Medicine"],["dc.bibliographiccitation.lastpage","1700"],["dc.bibliographiccitation.volume","98"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Reetz, Florian"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Shomroni, Orr"],["dc.contributor.author","Salinas, Gabriela"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Hammer, Karin P."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Hamdani, Nazha"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2021-04-14T08:32:15Z"],["dc.date.available","2021-04-14T08:32:15Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1007/s00109-020-01989-6"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83859"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1432-1440"],["dc.relation.issn","0946-2716"],["dc.title","Long-term effects of empagliflozin on excitation-contraction-coupling in human induced pluripotent stem cell cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1673"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","1685"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Eiringhaus, Jörg"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Saadatmand, Alireza"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Weber, Silvio"],["dc.contributor.author","Wang, Yansong"],["dc.contributor.author","Köhn, Maja"],["dc.contributor.author","Tirilomis, Theodor"],["dc.contributor.author","Ljubojevic, Senka"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2019-02-18T13:43:31Z"],["dc.date.available","2019-02-18T13:43:31Z"],["dc.date.issued","2018"],["dc.description.abstract","Background Disruption of Ca2+ homeostasis is a key pathomechanism in heart failure. CaMKII-dependent hyperphosphorylation of ryanodine receptors in the sarcoplasmic reticulum (SR) increases the arrhythmogenic SR Ca2+ leak and depletes SR Ca2+ stores. The contribution of conversely acting serine/threonine phosphatases [protein phosphatase 1 (PP1) and 2A (PP2A)] is largely unknown. Methods and results Human myocardium from three groups of patients was investigated: (i) healthy controls (non-failing, NF, n = 8), (ii) compensated hypertrophy (Hy, n = 16), and (iii) end-stage heart failure (HF, n = 52). Expression of PP1 was unchanged in Hy but greater in HF compared to NF while its endogenous inhibitor-1 (I-1) was markedly lower expressed in both compared to NF, suggesting increased total PP1 activity. In contrast, PP2A expression was lower in Hy and HF compared to NF. Ca2+ homeostasis was severely disturbed in HF compared to Hy signified by a higher SR Ca2+ leak, lower systolic Ca2+ transients as well as a decreased SR Ca2+ load. Inhibition of PP1/PP2A by okadaic acid increased SR Ca2+ load and systolic Ca2+ transients but severely aggravated diastolic SR Ca2+ leak and cellular arrhythmias in Hy. Conversely, selective activation of PP1 by a PP1-disrupting peptide (PDP3) in HF potently reduced SR Ca2+ leak as well as cellular arrhythmias and, importantly, did not compromise systolic Ca2+ release and SR Ca2+ load. Conclusion This study is the first to functionally investigate the role of PP1/PP2A for Ca2+ homeostasis in diseased human myocardium. Our data indicate that a modulation of phosphatase activity potently impacts Ca2+ cycling properties. An activation of PP1 counteracts increased kinase activity in heart failure and successfully seals the arrhythmogenic SR Ca2+ leak. It may thus represent a promising future antiarrhythmic therapeutic approach."],["dc.identifier.doi","10.1002/ejhf.1297"],["dc.identifier.pmid","30191648"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57579"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/232"],["dc.language.iso","en"],["dc.notes.status","final"],["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.issn","1879-0844"],["dc.relation.workinggroup","RG El-Armouche"],["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.relation.workinggroup","RG T. Fischer"],["dc.title","Activation of protein phosphatase 1 by a selective phosphatase disrupting peptide reduces sarcoplasmic reticulum Ca2+ leak in human heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","495"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","507"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Kolijn, Detmar"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Tian, Yanna"],["dc.contributor.author","Lódi, Mária"],["dc.contributor.author","Herwig, Melissa"],["dc.contributor.author","Carrizzo, Albino"],["dc.contributor.author","Zhazykbayeva, Saltanat"],["dc.contributor.author","Kovács, Árpád"],["dc.contributor.author","Fülöp, Gábor Á"],["dc.contributor.author","Falcão-Pires, Inês"],["dc.contributor.author","Reusch, Peter H"],["dc.contributor.author","Linthout, Sophie Van"],["dc.contributor.author","Papp, Zoltán"],["dc.contributor.author","van Heerebeek, Loek"],["dc.contributor.author","Vecchione, Carmine"],["dc.contributor.author","Maier, Lars S"],["dc.contributor.author","Ciccarelli, Michele"],["dc.contributor.author","Tschöpe, Carsten"],["dc.contributor.author","Mügge, Andreas"],["dc.contributor.author","Bagi, Zsolt"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Hamdani, Nazha"],["dc.date.accessioned","2021-04-14T08:30:10Z"],["dc.date.available","2021-04-14T08:30:10Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1093/cvr/cvaa123"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83132"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1755-3245"],["dc.relation.issn","0008-6363"],["dc.title","Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Gα oxidation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]