Herting, Jonas

[["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","719"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Artificial Organs"],["dc.bibliographiccitation.lastpage","726"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Kleinwächter, Astrid"],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Eiringhaus, Jörg"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Haverich, Axel"],["dc.contributor.author","Schmitto, Jan D."],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2018-11-07T10:10:45Z"],["dc.date.available","2018-11-07T10:10:45Z"],["dc.date.issued","2016"],["dc.description.abstract","In heart failure, left ventricular assist device (LVAD) implantation is performed to ensure sufficient cardiac output. Whereas some patients are subsequently weaned from LVAD support, other patients still need heart transplantation. To elucidate underlying mechanisms, we assessed the arrhythmogenic SR-Ca2+ leak at the time of LVAD implantation (HF-Im) and heart transplantation (HF-Tx) and evaluated the effects of CaMKII-inhibition. Human left-ventricular cardiomyocytes were isolated, paced at 1Hz for 10 beats to ensure SR-Ca2+ loading and scanned for diastolic Ca2+ sparks (confocal microscopy). In HF-Im, the high diastolic spark frequency (CaSpF) of 0.76 +/- 0.12x100m(-1)xs(-1) could be reduced to 0.48 +/- 0.10x100m(-1)xs(-1) by CaMKII inhibition (AIP, 1M). The amplitude of Ca2+ sparks, width, and length was not significantly altered. In sum, CaMKII inhibition yielded a clear tendency toward a reduction of the SR-Ca2+ leak (n cells/patients=76/6 vs. 108/6, P=0.08). In HF-Tx, we detected an even higher CaSpF of 1.00 +/- 0.10 100m(-1)xs(-1) and a higher SR-Ca2+ leak compared with HF-Im (increase by 81 +/- 33%, n cells/patients=156/7 vs. 130/7, P<0.05), which fits to the further decreased LV function. Here, CaMKII inhibition likewise reduced CaSpF (0.35 +/- 0.09 100m(-1)xs(-1,)P=0.06) and significantly reduced spark duration (n sparks/patients=58/3 vs. 159/3, P<0.05). Conclusively, the SR-Ca2+ leak was reduced by 69 +/- 12% in HF-Tx upon CaMKII inhibition (n cells/patients=53/3 vs. 91/3, P<0.05). These data show that the SR-Ca2+ leak correlates with the development of LV function after LVAD implantation and may represent an important pathomechanism. The fact that CaMKII inhibition reduces the SR-Ca2+ leak in HF-Tx suggests that CaMKII inhibition may be a promising option to beneficially influence clinical course after LVAD implantation."],["dc.identifier.doi","10.1111/aor.12677"],["dc.identifier.isi","000383514300005"],["dc.identifier.pmid","26816346"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39920"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/136"],["dc.language.iso","en"],["dc.notes.status","final"],["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.issn","1525-1594"],["dc.relation.issn","0160-564X"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.title","Inhibition of CaMKII Attenuates Progressing Disruption of Ca2+ Homeostasis Upon Left Ventricular Assist Device Implantation in Human Heart Failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Der Internist"],["dc.bibliographiccitation.volume","57"],["dc.contributor.author","Herting, J. Jonas"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Eiringhaus, Joerg"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Fischer, T."],["dc.date.accessioned","2018-11-07T10:15:51Z"],["dc.date.available","2018-11-07T10:15:51Z"],["dc.date.issued","2016"],["dc.format.extent","S20"],["dc.identifier.isi","000375417500035"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40900"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.issn","1432-1289"],["dc.relation.issn","0020-9554"],["dc.title","Influence of Atrial Fibrillation on the electromechanical Coupling in human Ventricular Myocardium"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","184"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","196"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Mason, Fleur E."],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Watanabe, Saera"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Sprenger, Julia U."],["dc.contributor.author","Fan, Peidong"],["dc.contributor.author","Yao, Lina"],["dc.contributor.author","Popov, Aron-Frederik"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Schoendube, Friedrich"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2017-09-07T11:43:42Z"],["dc.date.available","2017-09-07T11:43:42Z"],["dc.date.issued","2015"],["dc.description.abstract","Aims Enhanced cardiac late Na current (late I-Na) and increased sarcoplasmic reticulum (SR)-Ca2+-leak are both highly arrhythmogenic. This study seeks to identify signalling pathways interconnecting late I-Na and SR-Ca2+-leak in atrial cardiomyocytes (CMs). Methods and results In murine atrial CMs, SR-Ca2+-leak was increased by the late I-Na enhancer Anemonia sulcata toxin II (ATX-II). An inhibition of Ca2+/calmodulin-dependent protein kinase II (Autocamide-2-related inhibitory peptide), protein kinase A (H89), or late I-Na (Ranolazine or Tetrodotoxin) all prevented ATX-II-dependent SR-Ca2+-leak. The SR-Ca2+-leak induction by ATX-II was not detected when either the Na+/Ca2+ exchanger was inhibited (KBR) or in CaMKIIdc-knockout mice. FRET measurements revealed increased cAMP levels upon ATX-II stimulation, which could be prevented by inhibition of adenylyl cyclases (ACs) 5 and 6 (NKY 80) but not by inhibition of phosphodiesterases (IBMX), suggesting PKA activation via an AC-dependent increase of cAMP levels. Western blots showed late I-Na-dependent hyperphosphorylation of CaMKII as well as PKA target sites at ryanodine receptor type-2 (-S2814 and -S2808) and phospholamban (-Thr17, -S16). Enhancement of late I-Na did not alter Ca2+-transient amplitude or SR-Ca2+-load. However, upon late I-Na activation and simultaneous CaMKII inhibition, Ca2+-transient amplitude and SR-Ca2+-load were increased, whereas PKA inhibition reduced Ca2+-transient amplitude and load and additionally slowed Ca2+ elimination. In atrial CMs from patients with atrial fibrillation, inhibition of late I-Na, CaMKII, or PKA reduced the SR-Ca2+-leak. Conclusion Late I-Na exerts distinct effects on Ca2+ homeostasis in atrial myocardium through activation of CaMKII and PKA. Inhibition of late I-Na represents a potential approach to attenuate CaMKII activation and decreases SR-Ca2+-leak in atrial rhythm disorders. The interconnection with the cAMP/PKA system further increases the antiarrhythmic potential of late I-Na inhibition."],["dc.identifier.doi","10.1093/cvr/cvv153"],["dc.identifier.gro","3141867"],["dc.identifier.isi","000359088800021"],["dc.identifier.pmid","25990311"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1956"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/104"],["dc.language.iso","en"],["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 | A03: Bedeutung CaMKII-abhängiger Mechanismen für die Arrhythmogenese bei Herzinsuffizienz"],["dc.relation.eissn","1755-3245"],["dc.relation.issn","0008-6363"],["dc.relation.issn","1755-3245"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.title","Late INa increases diastolic SR-Ca2+-leak in atrial myocardium by activating PKA and CaMKII"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S10"],["dc.bibliographiccitation.journal","Der Internist"],["dc.bibliographiccitation.lastpage","S11"],["dc.bibliographiccitation.volume","57"],["dc.contributor.author","Pabel, Stefanie Corinna"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Herting, J. Jonas"],["dc.contributor.author","Fischer, T."],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel T."],["dc.date.accessioned","2018-11-07T10:15:53Z"],["dc.date.available","2018-11-07T10:15:53Z"],["dc.date.issued","2016"],["dc.identifier.isi","000375417500014"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40909"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.issn","1432-1289"],["dc.relation.issn","0020-9554"],["dc.title","Anti Arrhythmic Effects of Dantrolene in human Heart Failure and in Atrial Fibrillation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","1292"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","1300"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Eiringhaus, Jörg"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Foerster, Anna"],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Kleinwaechter, Astrid"],["dc.contributor.author","Ljubojevic, Senka"],["dc.contributor.author","Schmitto, Jan D."],["dc.contributor.author","Streckfuss-Boemeke, Katrin"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2017-09-07T11:45:23Z"],["dc.date.available","2017-09-07T11:45:23Z"],["dc.date.issued","2014"],["dc.description.abstract","AimsThe sarcoplasmic reticulum (SR) Ca2+ leak is an important pathomechanism in heart failure (HF). It has been suggested that Ca2+/calmodulin-dependent protein kinase II (CaMKII) is only relevant for the induction of the SR Ca2+ leak in non-ischaemic but not in ischaemic HF. Therefore, we investigated CaMKII and its targets as well as the functional effects of CaMKII inhibition in human ischaemic cardiomyopathy (ICM, n=37) and dilated cardiomyopathy (DCM, n=40). Methods and resultsWestern blots showed a significantly increased expression (by 549%) and autophosphorylation at Thr286 (by 129 +/- 29%, P<0.05 each) of CaMKII in HF compared with healthy myocardium. However, no significant difference could be detected in ICM compared with DCM as to the expression and autophosphorylation of CaMKII nor the phosphorylation of the target sites ryanodine receptor 2 (RyR2)-S2809, RyR2-S2815, and phospholamban-Thr17. Isolated human cardiomyocytes (CMs) of patients with DCM and ICM showed a similar frequency of diastolic Ca2+ sparks (confocal microscopy) as well as of major arrhythmic events (Ca2+ waves, spontaneous Ca2+ transients). Despite a slightly smaller size of Ca2+ sparks in DCM (P<0.01), the calculated SR Ca2+ leak [Ca2+ spark frequecy (CaSpF)xamplitudexwidthxduration] did not differ between CMs of ICM vs. DCM. Importantly, CaMKII inhibition by autocamide-2-related inhibitory peptide (AIP, 1 mu mol/L) reduced the SR Ca2+ leak by approximate to 80% in both aetiologies (P<0.05 each) and effectively decreased the ratio of arrhythmic cells (P<0.05). Conclusion

Functional and molecular measures of the SR Ca2+ leak are comparable in human ICM and DCM. CaMKII is equally responsible for the induction of the RyR2 leakiness' in both pathologies. Thus, CaMKII inhibition as a therapeutic measure may not be restricted to patients suffering from DCM but rather may be beneficial for the majority of HF patients."],["dc.identifier.doi","10.1002/ejhf.163"],["dc.identifier.gro","3142009"],["dc.identifier.isi","000345755200007"],["dc.identifier.pmid","25201344"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11676"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3534"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/15"],["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.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.eissn","1879-0844"],["dc.relation.issn","1388-9842"],["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.rights","CC BY-NC 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.title","Ca2+/calmodulin-dependent protein kinase II equally induces sarcoplasmic reticulum Ca2+ leak in human ischaemic and dilated cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Herting, J. Jonas"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Eiringhaus, Joerg"],["dc.contributor.author","Pabel, Stefanie Corinna"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Fischer, Thomas H."],["dc.date.accessioned","2018-11-07T10:14:46Z"],["dc.date.available","2018-11-07T10:14:46Z"],["dc.date.issued","2016"],["dc.format.extent","515"],["dc.identifier.isi","000377107504258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40681"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.issn","1879-0844"],["dc.relation.issn","1388-9842"],["dc.title","Effects of atrial fibrillation on ventricular calcium cycling in human myocardium"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","970"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.lastpage","981"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Tirilomis, Theodor"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Ellenberger, David"],["dc.contributor.author","Foerster, Anna"],["dc.contributor.author","Schmitto, Jan D."],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Schoendube, Friedrich A."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2017-09-07T11:47:37Z"],["dc.date.available","2017-09-07T11:47:37Z"],["dc.date.issued","2013"],["dc.description.abstract","Background Sarcoplasmic reticulum (SR) Ca2+ leak through ryanodine receptor type 2 (RyR2) dysfunction is of major pathophysiological relevance in human heart failure (HF); however, mechanisms underlying progressive RyR2 dysregulation from cardiac hypertrophy to HF are still controversial. Methods and Results We investigated healthy control myocardium (n=5) and myocardium from patients with compensated hypertrophy (n=25) and HF (n=32). In hypertrophy, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA) both phosphorylated RyR2 at levels that were not different from healthy myocardium. Accordingly, inhibitors of these kinases reduced the SR Ca2+ leak. In HF, however, the SR Ca2+ leak was nearly doubled compared with hypertrophy, which led to reduced systolic Ca2+ transients, a depletion of SR Ca2+ storage and elevated diastolic Ca2+ levels. This was accompanied by a significantly increased CaMKII-dependent phosphorylation of RyR2. In contrast, PKA-dependent RyR2 phosphorylation was not increased in HF and was independent of previous -blocker treatment. In HF, CaMKII inhibition but not inhibition of PKA yielded a reduction of the SR Ca2+ leak. Moreover, PKA inhibition further reduced SR Ca2+ load and systolic Ca2+ transients. Conclusions In human hypertrophy, both CaMKII and PKA functionally regulate RyR2 and may induce SR Ca2+ leak. In the transition from hypertrophy to HF, the diastolic Ca2+ leak increases and disturbed Ca2+ cycling occurs. This is associated with an increase in CaMKII- but not PKA-dependent RyR2 phosphorylation. CaMKII inhibition may thus reflect a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction."],["dc.identifier.doi","10.1161/CIRCULATIONAHA.113.001746"],["dc.identifier.gro","3142301"],["dc.identifier.isi","000323649600013"],["dc.identifier.pmid","23877259"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6764"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/14"],["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 | 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","0009-7322"],["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 Toischer (Kardiales Remodeling)"],["dc.title","Ca2+/Calmodulin-Dependent Protein Kinase II and Protein Kinase A Differentially Regulate Sarcoplasmic Reticulum Ca2+ Leak in Human Cardiac Pathology"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Eiringhaus, Joerg"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Herting, J. Jonas"],["dc.contributor.author","Schmitto, J."],["dc.contributor.author","Foerster, A."],["dc.contributor.author","Renner, Andre"],["dc.contributor.author","Gummert, J. F."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars. S."],["dc.contributor.author","Sossalla, Samuel T."],["dc.date.accessioned","2018-11-07T09:35:32Z"],["dc.date.available","2018-11-07T09:35:32Z"],["dc.date.issued","2014"],["dc.format.extent","328"],["dc.identifier.isi","000343001302012"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32409"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","Barcelona, SPAIN"],["dc.relation.issn","1522-9645"],["dc.relation.issn","0195-668X"],["dc.title","CaMKII equally triggers SR Ca2+leak in human ischemic and non-ischemic heart failure"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]