Herting, Jonas

[["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.artnumber","1"],["dc.bibliographiccitation.firstpage","2"],["dc.bibliographiccitation.journal","European Heart Journal - Case Reports"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Zabel, Markus"],["dc.contributor.author","Lüthje, Lars"],["dc.date.accessioned","2020-10-08T10:54:49Z"],["dc.date.accessioned","2021-10-27T13:22:20Z"],["dc.date.available","2020-10-08T10:54:49Z"],["dc.date.available","2021-10-27T13:22:20Z"],["dc.date.issued","2020"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2020"],["dc.identifier.doi","10.1093/ehjcr/ytaa244"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17588"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92086"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","2514-2119"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Pulmonary vein ablation in a patient with a large left common pulmonary vein joining a large right common trunk"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2992"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","ESC Heart Failure"],["dc.bibliographiccitation.lastpage","3002"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Eiringhaus, Jörg"],["dc.contributor.author","Wünsche, Christoph M."],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Bork, Nadja"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Fischer, Thomas H."],["dc.date.accessioned","2021-04-14T08:24:55Z"],["dc.date.available","2021-04-14T08:24:55Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Aims Inhibition of neprilysin and angiotensin II receptor by sacubitril/valsartan (Val) (LCZ696) reduces mortality in heart failure (HF) patients compared with sole inhibition of renin–angiotensin system. Beneficial effects of increased natriuretic peptide levels upon neprilysin inhibition have been proposed, whereas direct effects of sacubitrilat (Sac) (LBQ657) on myocardial Ca2+ cycling remain elusive. Methods and results Confocal microscopy (Fluo‐4 AM) was used to investigate pro‐arrhythmogenic sarcoplasmic reticulum (SR) Ca2+ leak in freshly isolated murine and human ventricular cardiomyocytes (CMs) upon Sac (40 μmol/L)/Val (13 μmol/L) treatment. The concentrations of Sac and Val equalled plasma concentrations of LCZ696 treatment used in PARADIGM‐HF trial. Epifluorescence microscopy measurements (Fura‐2 AM) were performed to investigate effects on systolic Ca2+ release, SR Ca2+ load, and Ca2+‐transient kinetics in freshly isolated murine ventricular CMs. The impact of Sac on myocardial contractility was evaluated using in toto‐isolated, isometrically twitching ventricular trabeculae from human hearts with end‐stage HF. Under basal conditions, the combination of Sac/Val did not influence diastolic Ca2+‐spark frequency (CaSpF) nor pro‐arrhythmogenic SR Ca2 leak in isolated murine ventricular CMs (n CMs/hearts = 80/7 vs. 100/7, P = 0.91/0.99). In contrast, Sac/Val treatment reduced CaSpF by 35 ± 9% and SR Ca2+ leak by 45 ± 9% in CMs put under catecholaminergic stress (isoproterenol 30 nmol/L, n = 81/7 vs. 62/7, P \\u0026lt; 0.001 each). This could be attributed to Sac, as sole Sac treatment also reduced both parameters by similar degrees (reduction of CaSpF by 57 ± 7% and SR Ca2+ leak by 76 ± 5%; n = 101/4 vs. 108/4, P \\u0026lt; 0.01 each), whereas sole Val treatment did not. Systolic Ca2+ release, SR Ca2+ load, and Ca2+‐transient kinetics including SERCA activity (kSERCA) were not compromised by Sac in isolated murine CMs (n = 41/6 vs. 39/6). Importantly, the combination of Sac/Val and Sac alone also reduced diastolic CaSpF and SR Ca2+ leak (reduction by 74 ± 7%) in human left ventricular CMs from patients with end‐stage HF (n = 71/8 vs. 78/8, P \\u0026lt; 0.05 each). Myocardial contractility of human ventricular trabeculae was not acutely affected by Sac treatment as the developed force remained unchanged over a time course of 30 min (n trabeculae/hearts = 3/3 vs. 4/3). Conclusion This study demonstrates that neprilysin inhibitor Sac directly improves Ca2+ homeostasis in human end‐stage HF by reducing pro‐arrhythmogenic SR Ca2+ leak without acutely affecting systolic Ca2+ release and inotropy. These effects might contribute to the mortality benefits observed in the PARADIGM‐HF trial."],["dc.description.sponsorship","Novartis http://dx.doi.org/10.13039/100004336"],["dc.description.sponsorship","Marga und Walter Boll‐Stiftung http://dx.doi.org/10.13039/501100011566"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1002/ehf2.12918"],["dc.identifier.pmid","32710603"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17698"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81465"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/363"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["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.eissn","2055-5822"],["dc.relation.issn","2055-5822"],["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 T. Fischer"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Sacubitrilat reduces pro‐arrhythmogenic sarcoplasmic reticulum Ca 2+ leak in human ventricular cardiomyocytes of patients with end‐stage heart failure"],["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","2850"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","2867"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Iyer, Lavanya M"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Woelfer, Monique"],["dc.contributor.author","Schoger, Eric"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Zafiriou, Maria Patapia"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Pang, Sze Ting"],["dc.contributor.author","Weber, Tobias"],["dc.contributor.author","Rathjens, Franziska S."],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Noack, Claudia"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Zelarayán, Laura C."],["dc.date.accessioned","2018-04-23T11:47:57Z"],["dc.date.available","2018-04-23T11:47:57Z"],["dc.date.issued","2018"],["dc.description.abstract","Chromatin remodelling precedes transcriptional and structural changes in heart failure. A body of work suggests roles for the developmental Wnt signalling pathway in cardiac remodelling. Hitherto, there is no evidence supporting a direct role of Wnt nuclear components in regulating chromatin landscapes in this process. We show that transcriptionally active, nuclear, phosphorylated(p)Ser675-β-catenin and TCF7L2 are upregulated in diseased murine and human cardiac ventricles. We report that inducible cardiomyocytes (CM)-specific pSer675-β-catenin accumulation mimics the disease situation by triggering TCF7L2 expression. This enhances active chromatin, characterized by increased H3K27ac and TCF7L2 occupancies to cardiac developmental and remodelling genes in vivo. Accordingly, transcriptomic analysis of β-catenin stabilized hearts shows a strong recapitulation of cardiac developmental processes like cell cycling and cytoskeletal remodelling. Mechanistically, TCF7L2 co-occupies distal genomic regions with cardiac transcription factors NKX2–5 and GATA4 in stabilized-β-catenin hearts. Validation assays revealed a previously unrecognized function of GATA4 as a cardiac repressor of the TCF7L2/β-catenin complex in vivo, thereby defining a transcriptional switch controlling disease progression. Conversely, preventing β-catenin activation post-pressure-overload results in a downregulation of these novel TCF7L2-targets and rescues cardiac function. Thus, we present a novel role for TCF7L2/β-catenin in CMs-specific chromatin modulation, which could be exploited for manipulating the ubiquitous Wnt pathway."],["dc.description.sponsorship","Open-Access-Publikatinsfonds 2018"],["dc.identifier.doi","10.1093/nar/gky049"],["dc.identifier.gro","3142314"],["dc.identifier.pmid","29394407"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15089"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13447"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/201"],["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 | 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","SFB 1002 | C07: Kardiomyozyten Wnt/β-catenin Komplex Aktivität im pathologischen Herz-Remodeling - als gewebespezifischer therapeutischer Ansatz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation","SFB 1002 | S02: Hochauflösende Fluoreszenzmikroskopie und integrative Datenanalyse"],["dc.relation","SFB 1002 | INF: Unterstützung der SFB 1002 Forschungsdatenintegration, -visualisierung und -nachnutzung"],["dc.relation.issn","0305-1048"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","A context-specific cardiac β-catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart"],["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.artnumber","e0167974"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLoS One"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Sprenger, Julia U."],["dc.contributor.author","Bork, Nadja I."],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.date.accessioned","2018-11-07T10:04:36Z"],["dc.date.available","2018-11-07T10:04:36Z"],["dc.date.issued","2016"],["dc.description.abstract","Calcium (Ca2+) and 3',5'-cyclic adenosine monophosphate (cAMP) play a critical role for cardiac excitation-contraction-coupling. Both second messengers are known to interact with each other, for example via Ca2+-dependent modulation of phosphodiesterase 1 (PDE1) and adenylyl cyclase 5/6 (AC 5/6) activities, which is supposed to occur especially at the local level in distinct subcellular microdomains. Currently, many studies analyze global and local cAMP signaling and its regulation in resting cardiomyocytes devoid of electrical stimulation. For example, Forster resonance energy transfer (FRET) microscopy is a popular approach for visualization of real time cAMP dynamics performed in resting cardiomyocytes to avoid potential contractility-related movement artifacts. However, it is unknown whether such data are comparable with the cell behavior under more physiologically relevant conditions during contraction. Here, we directly compare the cAMP-FRET responses to AC stimulation and PDE inhibition in resting vs. paced adult mouse ventricular cardiomyocytes for both cytosolic and subsarcolemmal microdomains. Interestingly, no significant differences in cAMP dynamics could be detected after beta-adrenergic (isoproterenol) stimulation, suggesting low impact of rapidly changing contractile Ca2+ concentrations on cytosolic cAMP levels associated with AC activation. However, the contribution of the calcium-dependent PDE1, but not of the Ca2+-insensitive PDE4, to the regulation of cAMP levels after forskolin stimulation was significantly increased. This increase could be mimicked by pretreatment of resting cells with Ca2+ elevating agents. Ca2+ imaging demonstrated significantly higher amplitudes of Ca2+ transients in forskolin than in isoproterenol stimulated cells, suggesting that forskolin stimulation might lead to stronger activation of PDE1. In conclusion, changes in intracellular Ca2+ during cardiomyocyte contraction dynamically interact with cAMP levels, especially after strong AC stimulation. The use of resting cells for FRET-based measurements of cAMP can be justified under beta-adrenergic stimulation, while the reliable analysis of PDE1 effects may require electric field stimulation."],["dc.identifier.doi","10.1371/journal.pone.0167974"],["dc.identifier.isi","000389580900066"],["dc.identifier.pmid","27930744"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14002"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38732"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/157"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A01: cAMP- und cGMP- Mikrodomänen bei Herzhypertrophie und Insuffizienz"],["dc.relation.issn","1932-6203"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Interactions of Calcium Fluctuations during Cardiomyocyte Contraction with Real-Time cAMP Dynamics Detected by FRET"],["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"]]