El-Armouche, Ali

[["dc.bibliographiccitation.firstpage","76"],["dc.bibliographiccitation.journal","Cellular Signalling"],["dc.bibliographiccitation.lastpage","84"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Weber, Silvio"],["dc.contributor.author","Zeller, Miriam"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Wunder, Frank"],["dc.contributor.author","Wagner, Michael"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2019-02-27T15:40:20Z"],["dc.date.available","2019-02-27T15:40:20Z"],["dc.date.issued","2017"],["dc.description.abstract","The cyclic nucleotides cAMP and cGMP are central second messengers in cardiac cells and critical regulators of cardiac physiology as well as pathophysiology. Consequently, subcellular compartmentalization allows for spatiotemporal control of cAMP/cGMP metabolism and subsequent regulation of their respective effector kinases PKA or PKG is most important for cardiac function in health and disease. While acute cAMP-mediated signalling is a mandatory prerequisite for the physiological fight-or-flight response and enhanced cardiac contractility and relaxation, sustained activation of this pathway may lead to the progression of heart failure. In contrast, acute as well as sustained cGMP-mediated signalling can foster beneficial features, e.g. anti-hypertrophic and vasodilatory effects and thus blunting some of the aforementioned cAMP-mediated effects. Although these two signalling pathways seem to be intuitively counteracting, there is increasing evidence for a functionally relevant crosstalk between cAMP and cGMP signalling pathways on the level of cyclic nucleotide hydrolysing phosphodiesterases (PDEs). Among this diverse group of enzymes, PDE2 fulfils a unique integrator role. Equipped with dual substrate specificity for cAMP as well as for cGMP, it is the only cAMP hydrolysing PDE, which is allosterically activated by cGMP. Recent studies have revealed strongly remodelled cAMP/cGMP microdomains and subcellular concentration profiles in different cardiac pathologies, leading to a putatively enhanced involvement of PDE2 in cAMP/cGMP breakdown and crosstalk compared to the other cardiac PDEs. This review sums up the current knowledge about molecular properties and regulation of PDE2 and explains the complex signalling network encompassing PDE2 in order to better understand the functional role of PDE2 in distinct cell types in cardiac health and disease. Moreover, this review gives an outlook in which way PDE2 may serve as a therapeutic target to treat cardiac diseases."],["dc.identifier.doi","10.1016/j.cellsig.2017.06.020"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57652"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/172"],["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","1873-3913"],["dc.relation.workinggroup","RG El-Armouche"],["dc.relation.workinggroup","RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)"],["dc.title","PDE2 at the crossway between cAMP and cGMP signalling in the heart"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","overview_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","165"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","175"],["dc.bibliographiccitation.volume","53"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Wittig, Karola"],["dc.contributor.author","Vogt, Andreas"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Wieland, Thomas"],["dc.date.accessioned","2018-11-07T09:07:59Z"],["dc.date.available","2018-11-07T09:07:59Z"],["dc.date.issued","2012"],["dc.description.abstract","Activation of alpha(1)-adrenoceptors (alpha(1)-AR) by high catecholamine levels, e.g. in heart failure, is thought to be a driving force of cardiac hypertrophy. In this context several downstream mediators and cascades have been identified to potentially play a role in cardiomyocyte hypertrophy. One of these proteins is the monomeric G protein Rac1. However, until now it is unclear how this essential G protein is activated by alpha(1)-AR agonists and what are the downstream targets inducing cellular growth. By using protein-based as well as pharmacological inhibitors and the shRNA technique, we demonstrate that in neonatal rat cardiomyocytes (NRCM) Rac1 is activated via a cascade involving the alpha(1A)-AR subtype, G(i)beta gamma, the phosphoinositide-3'-kinase and the guanine nucleotide exchange factor Tiam1. We further demonstrate that this signaling induces an increase in protein synthesis, cell size and atrial natriuretic peptide expression. We identified the p21-activated kinase 2 (PAK2) as a downstream effector of Rac1 and were able to link this cascade to the activation of the pro-hypertrophic kinases ERK1/2 and p90RSK. Our data thus reveal a prominent role of the alpha(1A)-AR/G(i)beta gamma/Tiam1-mediated activation of Rac1 and its effector PAK2 in the induction of hypertrophy in NRCM. (C) 2012 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2012.04.015"],["dc.identifier.isi","000306451600003"],["dc.identifier.pmid","22564263"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25922"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Ltd- Elsevier Science Ltd"],["dc.relation.issn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.title","A novel player in cellular hypertrophy: G(i)beta gamma/PI3K-dependent activation of the RacGEF TIAM-1 is required for alpha(1)-adrenoceptor induced hypertrophy in neonatal rat cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.volume","383"],["dc.contributor.author","Neuber, C."],["dc.contributor.author","Eder, Alexandra"],["dc.contributor.author","Hansen, A."],["dc.contributor.author","Mueller, Oliver J."],["dc.contributor.author","Sietmann, A."],["dc.contributor.author","Ruehle, Frank"],["dc.contributor.author","Stoll, Monika"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2018-11-07T08:58:33Z"],["dc.date.available","2018-11-07T08:58:33Z"],["dc.date.issued","2011"],["dc.format.extent","66"],["dc.identifier.isi","000288573100329"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23669"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","77th Annual Meeting on German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology"],["dc.relation.eventlocation","Frankfurt, GERMANY"],["dc.relation.issn","0028-1298"],["dc.title","AAV-mediated knockdown of the beta(1)-adrenoceptor in reconstituted heart tissue"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Neuber, C."],["dc.contributor.author","Uebeler, June"],["dc.contributor.author","Schulze, T."],["dc.contributor.author","Sotoud, Hannieh"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.date.accessioned","2018-11-07T09:37:38Z"],["dc.date.available","2018-11-07T09:37:38Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1093/cvr/cvu091.52"],["dc.identifier.isi","000343730100283"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32884"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.conference","3rd Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology"],["dc.relation.eventlocation","Barcelona, SPAIN"],["dc.relation.issn","1755-3245"],["dc.relation.issn","0008-6363"],["dc.title","Guanabenz interferes with ER stress and exerts protective effects in cardiac myocytes"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","13"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Gene Therapy"],["dc.bibliographiccitation.lastpage","19"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Schwab, D M"],["dc.contributor.author","Tilemann, L"],["dc.contributor.author","Bauer, R"],["dc.contributor.author","Heckmann, M"],["dc.contributor.author","Jungmann, A"],["dc.contributor.author","Wagner, M"],["dc.contributor.author","Burgis, J"],["dc.contributor.author","Vettel, C"],["dc.contributor.author","Katus, H A"],["dc.contributor.author","El-Armouche, A"],["dc.contributor.author","Müller, O J"],["dc.date.accessioned","2020-12-10T18:09:27Z"],["dc.date.available","2020-12-10T18:09:27Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1038/gt.2017.97"],["dc.identifier.eissn","1476-5462"],["dc.identifier.issn","0969-7128"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73660"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","AAV-9 mediated phosphatase-1 inhibitor-1 overexpression improves cardiac contractility in unchallenged mice but is deleterious in pressure-overload"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1150"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","U215"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Fluschnik, Nina"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Ort, Katharina R."],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Schulte, Timo"],["dc.contributor.author","Wittkoepper, Katrin"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Schmitto, Jan D."],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:45:15Z"],["dc.date.available","2017-09-07T11:45:15Z"],["dc.date.issued","2010"],["dc.description.abstract","Rationale: Heart failure (HF) is known to be associated with increased Ca2+/calmodulin-dependent protein kinase (CaMK)II expression and activity. There is still controversial discussion about the functional role of CaMKII in HF. Moreover, CaMKII inhibition has never been investigated in human myocardium. Objective: We sought to investigate detailed CaMKII delta expression in end-stage failing human hearts (dilated and ischemic cardiomyopathy) and the functional effects of CaMKII inhibition on contractility. Methods and Results: Expression analysis revealed that CaMKII delta, both cytosolic delta(C) and nuclear delta(B) splice variants, were significantly increased in both right and left ventricles from patients with dilated or ischemic cardiomyopathy versus nonfailing. Experiments with isometrically twitching trabeculae revealed significantly improved force frequency relationships in the presence of CaMKII inhibitors (KN-93 and AIP). Increased postrest twitches after CaMKII inhibition indicated an improved sarcoplasmic reticulum (SR) Ca2+ loading. This was confirmed in isolated myocytes by a reduced SR Ca2+ spark frequency and hence SR Ca2+ leak, resulting in increased SR Ca2+ load when inhibiting CaMKII. Ryanodine receptor type 2 phosphorylation at Ser2815, which is known to be phosphorylated by CaMKII thereby contributing to SR Ca2+ leak, was found to be markedly reduced in KN-93-treated trabeculae. Interestingly, CaMKII inhibition did not influence contractility in nonfailing sheep trabeculae. Conclusions: The present study shows for the first time that CaMKII inhibition acutely improves contractility in human HF where CaMKII delta expression is increased. The mechanism proposed consists of a reduced SR Ca2+ leak and consequently increased SR Ca2+ load. Thus, CaMKII inhibition appears to be a possible therapeutic option for patients with HF and merits further investigation. (Circ Res. 2010;107:1150-1161.)"],["dc.identifier.doi","10.1161/CIRCRESAHA.110.220418"],["dc.identifier.gro","3142840"],["dc.identifier.isi","000283583400015"],["dc.identifier.pmid","20814023"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6154"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/288"],["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","Lippincott Williams & Wilkins"],["dc.relation.issn","0009-7330"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Inhibition of Elevated Ca2+/Calmodulin-Dependent Protein Kinase II Improves Contractility in Human Failing Myocardium"],["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.artnumber","51"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","112"],["dc.contributor.author","Meyer-Roxlau, Stefanie"],["dc.contributor.author","Laemmle, Simon"],["dc.contributor.author","Opitz, Annett"],["dc.contributor.author","Kuenzel, Stephan"],["dc.contributor.author","Joos, Julius P."],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Sekeres, Karolina"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Schoendube, Friedrich"],["dc.contributor.author","Alexiou, Konstantin"],["dc.contributor.author","Maier, Lars. S."],["dc.contributor.author","Dobrev, Dobromir"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Weber, Silvio"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2018-11-07T10:21:50Z"],["dc.date.available","2018-11-07T10:21:50Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1007/s00395-017-0638-x"],["dc.identifier.isi","000404968800002"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42167"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","1435-1803"],["dc.relation.issn","0300-8428"],["dc.title","Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation (vol 112, pg 43, 2017)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","87"],["dc.bibliographiccitation.journal","IJC Heart & Vasculature"],["dc.bibliographiccitation.lastpage","94"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Friedrich, Felix W."],["dc.contributor.author","Sotoud, Hannieh"],["dc.contributor.author","Geertz, Birgit"],["dc.contributor.author","Weber, Silvio"],["dc.contributor.author","Flenner, Frederik"],["dc.contributor.author","Reischmann, Silke"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Carrier, Lucie"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2019-01-17T16:01:00Z"],["dc.date.available","2019-01-17T16:01:00Z"],["dc.date.issued","2015"],["dc.description.abstract","Aims Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy, diastolic dysfunction and increased interstitial fibrosis. Current treatment is based on beta-adrenoceptor (AR) and calcium channel blockers. Since mice deficient of protein phosphatase-1 inhibitor-1 (I-1), an amplifier in beta-AR signalling, were protected from pathological adrenergic stimulation in vivo, we hypothesized that I-1 ablation could result in an improved outcome in a HCM mouse model. Methods and results We crossed mice deficient of I-1 with homozygous myosin-binding protein C knock-out (Mybpc3 KO) mice exhibiting cardiac dilatation and reduced survival. Unexpectedly, survival time was shorter in double I-1/Mybpc3 KO than in single Mybpc3 KO mice. Longitudinal echocardiographic assessment revealed lower fractional area change, and higher diastolic left ventricular inner dimensions and end-diastolic volumes in Mybpc3 KO than in WT mice. In comparison to Mybpc3 KO, double I-1/Mybpc3 KO presented higher left ventricular end-diastolic volumes, inner dimensions and ventricular surface areas with increasing differences over time. Phosphorylation levels of PKA-downstream targets and mRNA levels of hypertrophic markers did not differ between I-1/Mybpc3 KO and single Mybpc3 KO mice, except a trend towards higher beta-myosin heavy chain levels in double I-1/Mybpc3 KO. Conclusion The data indicate that interference with beta-AR signalling has no long-term benefit in this severe MYBPC3-related cardiomyopathy mouse model."],["dc.identifier.doi","10.1016/j.ijcha.2015.05.010"],["dc.identifier.pmid","28785686"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57350"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/87"],["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","2352-9067"],["dc.relation.workinggroup","RG El-Armouche"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","I-1-deficiency negatively impacts survival in a cardiomyopathy mouse model"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]