Wagner, Stefan

[["dc.bibliographiccitation.firstpage","263"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.lastpage","272"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Maurer, Ulrike"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Hartmann, Nico H."],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:44:20Z"],["dc.date.available","2017-09-07T11:44:20Z"],["dc.date.issued","2011"],["dc.description.abstract","Transgenic (TG) Ca2+/calmodulin-dependent protein kinase II (CaMKII) delta(C) mice develop systolic heart failure (HF). CaMKII regulates intracellular Ca2+ handling proteins as well as sarcolemmal Na+ channels. We hypothesized that CaMKII also contributes to diastolic dysfunction and arrhythmias via augmentation of the late Na+ current (late I (Na)) in early HF (8-week-old TG mice). Echocardiography revealed severe diastolic dysfunction in addition to decreased systolic ejection fraction. Premature arrhythmogenic contractions (PACs) in isolated isometrically twitching papillary muscles only occurred in TG preparations (5 vs. 0, P < 0.05) which could be completely terminated when treated with the late I (Na) inhibitor ranolazine (Ran, 5 mu mol/L). Force-frequency relationships revealed significantly reduced twitch force amplitudes in TG papillary muscles. Most importantly, diastolic tension increased with raising frequencies to a greater extent in TG papillary muscles compared to WT specimen (at 10 Hz: 3.7 +/- A 0.4 vs. 2.5 +/- A 0.3 mN/mm(2); P < 0.05). Addition of Ran improved diastolic dysfunction to 2.1 +/- A 0.2 mN/mm(2) (at 10 Hz; P < 0.05) without negative inotropic effects. Mechanistically, the late I (Na) was markedly elevated in myocytes isolated from TG mice and could be completely reversed by Ran. In conclusion, our results show for the first time that TG CaMKII delta(C) overexpression induces diastolic dysfunction and arrhythmogenic triggers possibly via an enhanced late I (Na). Inhibition of elevated late I (Na) had beneficial effects on arrhythmias as well as diastolic function in papillary muscles from CaMKII delta(C) TG mice. Thus, late I (Na) inhibition appears to be a promising option for diastolic dysfunction and arrhythmias in HF where CaMKII is found to be increased."],["dc.identifier.doi","10.1007/s00395-010-0136-x"],["dc.identifier.gro","3142765"],["dc.identifier.isi","000286934300008"],["dc.identifier.pmid","21174213"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7315"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/205"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","0300-8428"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Diastolic dysfunction and arrhythmias caused by overexpression of CaMKII delta(C) can be reversed by inhibition of late Na+ current"],["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","726"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Diabetologia"],["dc.bibliographiccitation.lastpage","729"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Lücht, Charlotte M."],["dc.contributor.author","Wagemann, Olivia"],["dc.contributor.author","Sowa, Thomas"],["dc.contributor.author","Hammer, Karin P."],["dc.contributor.author","Sag, Can M."],["dc.contributor.author","Tarnowski, Daniel"],["dc.contributor.author","Holzamer, Andreas"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Beuthner, Bo Eric"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Wagner, Stefan"],["dc.date.accessioned","2019-07-09T11:51:32Z"],["dc.date.available","2019-07-09T11:51:32Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s00125-019-4819-z"],["dc.identifier.pmid","30694352"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16145"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59964"],["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","Empagliflozin enhances human and murine cardiomyocyte glucose uptake by increased expression of GLUT1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","20"],["dc.bibliographiccitation.journal","Frontiers in Pharmacology"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Wagner, Stefan"],["dc.date.accessioned","2018-11-07T09:43:39Z"],["dc.date.available","2018-11-07T09:43:39Z"],["dc.date.issued","2014"],["dc.description.abstract","Cardiac K channels are critical determinants of cardiac excitability. In hypertrophied and failing myocardium, alterations in the expression and activity of voltage-gated K channels are frequently observed and contribute to the increased propensity for life-threatening arrhythmias. Thus, understanding the mechanisms of disturbed K channel regulation in heart failure (HF) is of critical importance. Amongst others, Ca/calmodulin-dependent protein kinase II (CaMKII) has been identified as an important regulator of K channel activity. In human HF but also various animal models, increased CaMKI I expression and activity has been linked to deteriorated contractile function and arrhythmias. This review will discuss the current knowledge about CaMKII regulation of several K channels, its influence on action potential properties, dispersion of repolanzation, and arrhythmias with special focus on HF"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.3389/fphar.2014.00020"],["dc.identifier.isi","000347047500001"],["dc.identifier.pmid","24600393"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9943"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34226"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/39"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A03: Bedeutung CaMKII-abhängiger Mechanismen für die Arrhythmogenese bei Herzinsuffizienz"],["dc.relation.eissn","1663-9812"],["dc.relation.issn","1663-9812"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","CaMKII regulation of cardiac K channels"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","overview_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2330"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","2342"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Kallmeyer, Birte"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Mazur, Marek"],["dc.contributor.author","Maurer, Ulrike"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Schmitto, Jan D."],["dc.contributor.author","Seipelt, Ralf"],["dc.contributor.author","Schoendube, Friedrich A."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:46:03Z"],["dc.date.available","2017-09-07T11:46:03Z"],["dc.date.issued","2010"],["dc.description.abstract","Objectives We investigated changes in Na+ currents (I-Na) in permanent (or chronic) atrial fibrillation (AF) and the effects of I-Na inhibition using ranolazine (Ran) on arrhythmias and contractility in human atrial myocardium. Background Electrical remodeling during AF is typically associated with alterations in Ca2+ and K+ currents. It remains unclear whether I-Na is also altered. Methods Right atrial appendages from patients with AF (n = 23) and in sinus rhythm (SR) (n = 79) were studied. Results Patch-clamp experiments in isolated atrial myocytes showed significantly reduced peak I-Na density (similar to 16%) in AF compared with SR, which was accompanied by a 26% lower expression of Nav1.5 (p < 0.05). In contrast, late I-Na was significantly increased in myocytes from AF atria by similar to 26%. Ran (10 mu mol/l) decreased late I-Na by similar to 60% (p < 0.05) in myocytes from patients with AF but only by similar to 18% (p < 0.05) in myocytes from SR atria. Proarrhythmic activity was elicited in atrial trabeculae exposed to high [Ca2+](o) or isoprenaline, which was significantly reversed by Ran (by 83% and 100%, respectively). Increasing pacing rates from 0.5 to 3.0 Hz led to an increase in diastolic tension that could be significantly decreased by Ran in atria from SR and AF patients. Conclusions Na+ channels may contribute to arrhythmias and contractile remodeling in AF. Inhibition of I-Na with Ran had antiarrhythmic effects and improved diastolic function. Thus, inhibition of late I-Na may be a promising new treatment option for patients with atrial rhythm disturbances and diastolic dysfunction. (J Am Coll Cardiol 2010;55:2330-42) (C) 2010 by the American College of Cardiology Foundation"],["dc.identifier.doi","10.1016/j.jacc.2009.12.055"],["dc.identifier.gro","3142922"],["dc.identifier.isi","000277805800007"],["dc.identifier.pmid","20488304"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6156"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/379"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: DFG [MA1982/4-1]; Klinische Forschergruppe [MA1982/2-2]; CV Therapeutics"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0735-1097"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Altered Na+ Currents in Atrial Fibrillation Effects of Ranolazine on Arrhythmias and Contractility in Human Atrial Myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","33"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","42"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Seidler, Tim"],["dc.contributor.author","Teucher, Nils"],["dc.contributor.author","Hellenkamp, Kristian"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Grebe, Cornelia"],["dc.contributor.author","Kramps, Petra"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Schoendube, Friedrich A."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:45:07Z"],["dc.date.available","2017-09-07T11:45:07Z"],["dc.date.issued","2011"],["dc.description.abstract","Sarcoplasmic reticulum (SR) calcium (Ca) leak can be reduced by enhancing FKBP12.6 binding to SR Ca release channels (RyR2) and expression of a \"sticky\" FKBP12.6(D37s) mutant may correct reduced binding stoichiometry in RyR2 from failing hearts. Both calcium/calmodulin-dependent protein kinase II delta c (CaMKII delta c) and protein kinase A (PKA) are activated in heart failure and promote SR Ca leak at RyR2. It is possible that FKBP12.6 dissociation from RyR2 may promote remodeling and that interventions to reassociate FKBP12.6 with RyR2 reflect a future therapeutic strategy. We created transgenic (TG) mice expressing FKBP12.6(D37s) and tested their capacity to improve intracellular Ca handling and pathological remodeling in vivo. FKBP12.6(D37S) TG mice were cross-bred with CaMKII delta c TG mice, which are known to exhibit pronounced RyR2 dysfunction and heart failure. We observed a significant improvement of post-rest Ca transients and a higher SR Ca content in FKBP12.6(D37S) TG mice. In double-TG mice, a marked reduction of SR Ca spark frequency indicated reduced SR Ca leak but neither SR Ca transient amplitude, SR Ca content nor morphological or functional parameters improved in vivo. Likewise, FKBP12.6(D37s) TG mice subjected to increased afterload after aortic banding exhibited higher SR Ca load but did not exhibit any improvement in hypertrophic growth or functional decline. Enhancement of FKBP12.6-RyR2 binding markedly reduced RyR2 Ca leak in CaMKII delta c-induced heart failure and in pressure overload. Our data suggest that activation of CaMKII delta c and pressure overload confer significant resistance towards approaches aiming at FKBP12.6-RyR2 reconstitution in heart failure and maladaptive remodeling, although RyR2 Ca leak can be reduced. (C) 2010 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2010.08.016"],["dc.identifier.gro","3142803"],["dc.identifier.isi","000286502800008"],["dc.identifier.pmid","20797399"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6309"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/248"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["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.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Limitations of FKBP12.6-directed treatment strategies for maladaptive cardiac remodeling and heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]