Dewenter, Matthias

[["dc.bibliographiccitation.firstpage","599a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Lindner, Marta"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Dewenter, Matthias"],["dc.contributor.author","Riedel, Merle"],["dc.contributor.author","Lämmle, Simon"],["dc.contributor.author","Mason, Fleur"],["dc.contributor.author","Meinecke, Simon"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Mehel, Hind"],["dc.contributor.author","Karam, Sarah"],["dc.contributor.author","Lechene, Patrick"],["dc.contributor.author","Leroy, Jerome"],["dc.contributor.author","Vandecasteele, Gregoire"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Fischmeister, Rodolphe"],["dc.date.accessioned","2020-12-10T14:22:42Z"],["dc.date.available","2020-12-10T14:22:42Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1016/j.bpj.2015.11.3199"],["dc.identifier.issn","0006-3495"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71701"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Cardiac-Specific Overexpression of Phosphodiesterase 2 (PDE2) in Mouse is Cardioprotective"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1596"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","1606"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Mehel, Hind"],["dc.contributor.author","Emons, Julius"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Wittköpper, Katrin"],["dc.contributor.author","Seppelt, Danilo"],["dc.contributor.author","Dewenter, Matthias"],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Lechêne, Patrick"],["dc.contributor.author","Leroy, Jérôme"],["dc.contributor.author","Lefebvre, Florence"],["dc.contributor.author","Varin, Audrey"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Nattel, Stanley"],["dc.contributor.author","Dobrev, Dobromir"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Vandecasteele, Grégoire"],["dc.contributor.author","Fischmeister, Rodolphe"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2019-01-14T16:02:22Z"],["dc.date.available","2019-01-14T16:02:22Z"],["dc.date.issued","2013"],["dc.description.abstract","Objectives This study investigated whether myocardial phosphodiesterase-2 (PDE2) is altered in heart failure (HF) and determined PDE2-mediated effects on beta-adrenergic receptor (β-AR) signaling in healthy and diseased cardiomyocytes. Background Diminished cyclic adenosine monophosphate (cAMP) and augmented cyclic guanosine monophosphate (cGMP) signaling is characteristic for failing hearts. Among the PDE superfamily, PDE2 has the unique property of being able to be stimulated by cGMP, thus leading to a remarkable increase in cAMP hydrolysis mediating a negative cross talk between cGMP and cAMP signaling. However, the role of PDE2 in HF is poorly understood. Methods Immunoblotting, radioenzymatic- and fluorescence resonance energy transfer–based assays, video edge detection, epifluorescence microscopy, and L-type Ca2+ current measurements were performed in myocardial tissues and/or isolated cardiomyocytes from human and/or experimental HF, respectively. Results Myocardial PDE2 expression and activity were ∼2-fold higher in advanced human HF. Chronic β-AR stimulation via catecholamine infusions in rats enhanced PDE2 expression ∼2-fold and cAMP hydrolytic activity ∼4-fold, which correlated with blunted cardiac β-AR responsiveness. In diseased cardiomyocytes, higher PDE2 activity could be further enhanced by stimulation of cGMP synthesis via nitric oxide donors, whereas specific PDE2 inhibition partially restored β-AR responsiveness. Accordingly, PDE2 overexpression in healthy cardiomyocytes reduced the rise in cAMP levels and L-type Ca2+ current amplitude, and abolished the inotropic effect following acute β-AR stimulation, without affecting basal contractility. Importantly, PDE2-overexpressing cardiomyocytes showed marked protection from norepinephrine-induced hypertrophic responses. Conclusions PDE2 is markedly up-regulated in failing hearts and desensitizes against acute β-AR stimulation. This may constitute an important defense mechanism during cardiac stress, for example, by antagonizing excessive β-AR drive. Thus, activating myocardial PDE2 may represent a novel intracellular antiadrenergic therapeutic strategy in HF."],["dc.identifier.doi","10.1016/j.jacc.2013.05.057"],["dc.identifier.gro","3142269"],["dc.identifier.isi","000325937400010"],["dc.identifier.pmid","23810893"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57317"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/37"],["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 | A01: cAMP- und cGMP- Mikrodomänen bei Herzhypertrophie und Insuffizienz"],["dc.relation","SFB 1002 | A02: Bedeutung des Phosphatase-Inhibitors-1 für die SR-spezifische Modulation der Beta- adrenozeptor-Signalkaskade"],["dc.relation","SFB 1002 | C02: RhoGTPasen und ihre Bedeutung für die Last-abhängige Myokardfibrose"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation.eissn","1558-3597"],["dc.relation.issn","1558-3597"],["dc.relation.issn","0735-1097"],["dc.relation.workinggroup","RG El-Armouche"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["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 Zimmermann (Engineered Human Myocardium)"],["dc.title","Phosphodiesterase-2 Is Up-Regulated in Human Failing Hearts and Blunts β-Adrenergic Responses in Cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","819"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Heart"],["dc.bibliographiccitation.lastpage","820"],["dc.bibliographiccitation.volume","100"],["dc.contributor.author","Dewenter, Matthias"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2019-02-05T10:29:11Z"],["dc.date.available","2019-02-05T10:29:11Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1136/heartjnl-2014-305503"],["dc.identifier.pmid","24667282"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57520"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/9"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A02: Bedeutung des Phosphatase-Inhibitors-1 für die SR-spezifische Modulation der Beta- adrenozeptor-Signalkaskade"],["dc.relation.issn","1468-201X"],["dc.relation.workinggroup","RG El-Armouche"],["dc.title","The Janus face of BNP therapy in chronic heart failure: beneficial effects unmasked by β blockers?"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","editorial_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e003840"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Circulation: Heart Failure"],["dc.bibliographiccitation.lastpage","9"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Dewenter, Matthias"],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Lämmle, Simon"],["dc.contributor.author","Beushausen, Christina"],["dc.contributor.author","Zelarayan, Laura C."],["dc.contributor.author","Katz, Sylvia"],["dc.contributor.author","von der Lieth, Albert"],["dc.contributor.author","Meyer-Roxlau, Stefanie"],["dc.contributor.author","Weber, Silvio"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Backs, Johannes"],["dc.contributor.author","Brown, Joan H."],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2020-12-10T18:37:57Z"],["dc.date.available","2020-12-10T18:37:57Z"],["dc.date.issued","2017"],["dc.description.abstract","Background— Considerable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), a condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate a significant cross talk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β-AR signaling in HF. In this study, we investigated the effect of chronic β-AR blocker treatment on CaMKII activity in human and experimental HF. Methods and Results— Immunoblot analysis of myocardium from end-stage HF patients (n=12) and non-HF subjects undergoing cardiac surgery (n=12) treated with β-AR blockers revealed no difference in CaMKII activity when compared with non–β-AR blocker–treated patients. CaMKII activity was judged by analysis of CaMKII expression, autophosphorylation, and oxidation and by investigating the phosphorylation status of CaMKII downstream targets. To further evaluate these findings, CaMKIIδC transgenic mice were treated with the β1-AR blocker metoprolol (270 mg/kg d). Metoprolol significantly reduced transgene-associated mortality (n≥29; P<0.001), attenuated the development of cardiac hypertrophy (−14±6% heart weight/tibia length; P<0.05), and strongly reduced ventricular arrhythmias (−70±22% premature ventricular contractions; P<0.05). On a molecular level, metoprolol expectedly decreased protein kinase A–dependent phospholamban and ryanodine receptor 2 phosphorylation (−42±9% for P-phospholamban-S16 and −22±7% for P-ryanodine receptor 2-S2808; P<0.05). However, this was paralled neither by a reduction in CaMKII autophosphorylation, oxidation, and substrate binding nor a change in the phosphorylation of CaMKII downstream target proteins (n≥11). The lack of CaMKII modulation by β-AR blocker treatment was confirmed in healthy wild-type mice receiving metoprolol. Conclusions— Chronic β-AR blocker therapy in patients and in a mouse model of CaMKII-induced HF is not associated with a change in CaMKII activity. Thus, our data suggest that the molecular effects of β-AR blockers are not based on a modulation of CaMKII. Directly targeting CaMKII may, therefore, further improve HF therapy in addition to β-AR blockade."],["dc.identifier.doi","10.1161/CIRCHEARTFAILURE.117.003840"],["dc.identifier.pmid","28487342"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77149"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/171"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A02: Bedeutung des Phosphatase-Inhibitors-1 für die SR-spezifische Modulation der Beta- adrenozeptor-Signalkaskade"],["dc.relation","SFB 1002 | A03: Bedeutung CaMKII-abhängiger Mechanismen für die Arrhythmogenese bei Herzinsuffizienz"],["dc.relation.issn","1941-3289"],["dc.relation.issn","1941-3297"],["dc.relation.workinggroup","RG El-Armouche"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.title","Calcium/Calmodulin-Dependent Protein Kinase II Activity Persists During Chronic β-Adrenoceptor Blockade in Experimental and Human Heart Failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S67"],["dc.bibliographiccitation.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.lastpage","S68"],["dc.bibliographiccitation.volume","387"],["dc.contributor.author","Meyer-Roxlau, Stefanie"],["dc.contributor.author","Dewenter, Matthias"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2018-11-07T09:44:49Z"],["dc.date.available","2018-11-07T09:44:49Z"],["dc.date.issued","2014"],["dc.identifier.isi","000359538500273"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34478"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","80th Annual Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und Toxikologie-e-V"],["dc.relation.eventlocation","Hannover, GERMANY"],["dc.relation.issn","1432-1912"],["dc.relation.issn","0028-1298"],["dc.title","Development of molecular imaging tools to investigate protein phosphatase type-1 and type-2A localisation and dynamics in living cells"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.volume","387"],["dc.contributor.author","Saadatmand, Ali Reza"],["dc.contributor.author","Dewenter, Matthias"],["dc.contributor.author","Meyer-Roxlau, Stefanie"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Lehmann, Lorenz H."],["dc.contributor.author","Backs, Johannes"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2018-11-07T09:44:50Z"],["dc.date.available","2018-11-07T09:44:50Z"],["dc.date.issued","2014"],["dc.format.extent","S80"],["dc.identifier.isi","000359538500325"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34485"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","80th Annual Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und Toxikologie-e-V"],["dc.relation.eventlocation","Hannover, GERMANY"],["dc.relation.issn","1432-1912"],["dc.relation.issn","0028-1298"],["dc.title","PKA and CaMKII- mediated phosphorylation of Histone H3S28 during pathological b-adrenergic stimulation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","15"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Dewenter, Matthias"],["dc.contributor.author","Pan, Jianyuan"],["dc.contributor.author","Knödler, Laura"],["dc.contributor.author","Tzschöckel, Niklas"],["dc.contributor.author","Henrich, Julian"],["dc.contributor.author","Cordero, Julio"],["dc.contributor.author","Dobreva, Gergana"],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Backs, Johannes"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Vettel, Christiane"],["dc.date.accessioned","2022-04-01T10:01:09Z"],["dc.date.available","2022-04-01T10:01:09Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract Hyperactivity of the sympathetic nervous system is a major driver of cardiac remodeling, exerting its effects through both α-, and β-adrenoceptors (α-, β-ARs). As the relative contribution of subtype α 1 -AR to cardiac stress responses remains poorly investigated, we subjected mice to either subcutaneous perfusion with the β-AR agonist isoprenaline (ISO, 30 mg/kg × day) or to a combination of ISO and the stable α 1 -AR agonist phenylephrine (ISO/PE, 30 mg/kg × day each). Telemetry analysis revealed similar hemodynamic responses under both ISO and ISO/PE treatment i.e., permanently increased heart rates and only transient decreases in mean blood pressure during the first 24 h. Echocardiography and single cell analysis after 1 week of exposure showed that ISO/PE-, but not ISO-treated animals established α 1 -AR-mediated inotropic responsiveness to acute adrenergic stimulation. Morphologically, additional PE perfusion limited concentric cardiomyocyte growth and enhanced cardiac collagen deposition during 7 days of treatment. Time-course analysis demonstrated a diverging development in transcriptional patterns at day 4 of treatment i.e., increased expression of selected marker genes Xirp2, Nppa, Tgfb1, Col1a1, Postn under chronic ISO/PE treatment which was either less pronounced or absent in the ISO group. Transcriptome analyses at day 4 via RNA sequencing demonstrated that additional PE treatment caused a marked upregulation of genes allocated to extracellular matrix and fiber organization along with a more pronounced downregulation of genes involved in metabolic processes, muscle adaptation and cardiac electrophysiology. Consistently, transcriptome changes under ISO/PE challenge more effectively recapitulated early transcriptional alterations in pressure overload-induced experimental heart failure and in human hypertrophic cardiomyopathy."],["dc.identifier.doi","10.1007/s00395-022-00920-z"],["dc.identifier.pii","920"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105612"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1435-1803"],["dc.relation.issn","0300-8428"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Chronic isoprenaline/phenylephrine vs. exclusive isoprenaline stimulation in mice: critical contribution of alpha1-adrenoceptors to early cardiac stress responses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","120"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","132"],["dc.bibliographiccitation.volume","120"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Lindner, Marta"],["dc.contributor.author","Dewenter, Matthias"],["dc.contributor.author","Lorenz, Kristina"],["dc.contributor.author","Schanbacher, Constanze"],["dc.contributor.author","Riedel, Merle"],["dc.contributor.author","Lämmle, Simon"],["dc.contributor.author","Meinecke, Simone"],["dc.contributor.author","Mason, Fleur E."],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Geerts, Andreas"],["dc.contributor.author","Hoffmann, Michael"],["dc.contributor.author","Wunder, Frank"],["dc.contributor.author","Brunner, Fabian J."],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Mehel, Hind"],["dc.contributor.author","Karam, Sarah"],["dc.contributor.author","Lechêne, Patrick"],["dc.contributor.author","Leroy, Jérôme"],["dc.contributor.author","Vandecasteele, Grégoire"],["dc.contributor.author","Wagner, Michael"],["dc.contributor.author","Fischmeister, Rodolphe"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2020-12-10T18:37:59Z"],["dc.date.available","2020-12-10T18:37:59Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1161/CIRCRESAHA.116.310069"],["dc.identifier.pmid","27799254"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77159"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/309"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A02: Bedeutung des Phosphatase-Inhibitors-1 für die SR-spezifische Modulation der Beta- adrenozeptor-Signalkaskade"],["dc.relation.workinggroup","RG El-Armouche"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.title","Phosphodiesterase 2 Protects Against Catecholamine-Induced Arrhythmia and Preserves Contractile Function After Myocardial Infarction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.volume","388"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Dewenter, Matthias"],["dc.contributor.author","Linder, M."],["dc.contributor.author","Riedel, Michael"],["dc.contributor.author","Laemmle, Simon"],["dc.contributor.author","Mason, F."],["dc.contributor.author","Meinecke, S."],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Vandecasteele, Gregoire"],["dc.contributor.author","Geerts, A."],["dc.contributor.author","Wunderlich, F. Thomas"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Fischmeister, Rodolphe"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2018-11-07T10:01:10Z"],["dc.date.available","2018-11-07T10:01:10Z"],["dc.date.issued","2015"],["dc.format.extent","S42"],["dc.identifier.isi","000359539100167"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37959"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","81st Annual Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und Toxikologie-e-V"],["dc.relation.eventlocation","Kiel, GERMANY"],["dc.relation.issn","1432-1912"],["dc.relation.issn","0028-1298"],["dc.title","Phosphodiesterase 2 regulates resting heart rate and protects against arrhythmias and beta-adrenergic overstimulation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","H1246"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","American Journal of Physiology - Heart and Circulatory Physiology"],["dc.bibliographiccitation.lastpage","H1252"],["dc.bibliographiccitation.volume","306"],["dc.contributor.author","Vettel, C."],["dc.contributor.author","Lämmle, S."],["dc.contributor.author","Ewens, S."],["dc.contributor.author","Cervirgen, C."],["dc.contributor.author","Emmons, J."],["dc.contributor.author","Ongherth, A."],["dc.contributor.author","Dewenter, M."],["dc.contributor.author","Lindner, D."],["dc.contributor.author","Westermann, D."],["dc.contributor.author","Nikolaev, V. O."],["dc.contributor.author","Lutz, S."],["dc.contributor.author","Zimmermann, W.-H."],["dc.contributor.author","El-Armouche, A."],["dc.date.accessioned","2017-09-07T11:46:22Z"],["dc.date.available","2017-09-07T11:46:22Z"],["dc.date.issued","2014"],["dc.description.abstract","Recent studies suggest that the signal molecules cAMP and cGMP have antifibrotic effects by negatively regulating pathways associated with fibroblast to myofibroblast (MyoCF) conversion. The phosphodiesterase 2 (PDE2) has the unique property to be stimulated by cGMP, which leads to a remarkable increase in cAMP hydrolysis and thus mediates a negative cross-talk between both pathways. PDE2 has been recently investigated in cardiomyocytes; here we specifically addressed its role in fibroblast conversion and cardiac fibrosis. PDE2 is abundantly expressed in both neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes. The overexpression of PDE2 in CFs strongly reduced basal and isoprenaline-induced cAMP synthesis, and this decrease was sufficient to induce MyoCF conversion even in the absence of exogenous profibrotic stimuli. Functional stress-strain experiments with fibroblast-derived engineered connective tissue (ECT) demonstrated higher stiffness in ECTs overexpressing PDE2. In regard to cGMP, neither basal nor atrial natriuretic peptide-induced cGMP levels were affected by PDE2, whereas the response to nitric oxide donor sodium nitroprusside was slightly but significantly reduced. Interestingly, despite persistently depressed cAMP levels, both cGMP-elevating stimuli were able to completely prevent the PDE2-induced MyoCF phenotype, arguing for a double-tracked mechanism. In conclusion, PDE2 accelerates CF to MyoCF conversion, which leads to greater stiffness in ECTs. Atrial natriuretic peptide-and sodium nitroprusside-mediated cGMP synthesis completely reverses PDE2-induced fibroblast conversion. Thus PDE2 may augment cardiac remodeling, but this effect can also be overcome by enhanced cGMP. The redundant role of cAMP and cGMP as antifibrotic meditators may be viewed as a protective mechanism in heart failure."],["dc.identifier.doi","10.1152/ajpheart.00852.2013"],["dc.identifier.gro","3142154"],["dc.identifier.isi","000334596500016"],["dc.identifier.pmid","24531807"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5133"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/67"],["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 | A02: Bedeutung des Phosphatase-Inhibitors-1 für die SR-spezifische Modulation der Beta- adrenozeptor-Signalkaskade"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation.eissn","1522-1539"],["dc.relation.issn","0363-6135"],["dc.relation.workinggroup","RG El-Armouche"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.title","PDE2-mediated cAMP hydrolysis accelerates cardiac fibroblast to myofibroblast conversion and is antagonized by exogenous activation of cGMP signaling pathways"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]