Lutz, Susanne

[["dc.bibliographiccitation.firstpage","1261"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Cellular Signalling"],["dc.bibliographiccitation.lastpage","1269"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Carbajo-Lozoya, Javier"],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Feng, Yuxi"],["dc.contributor.author","Kroll, Jens"],["dc.contributor.author","Hammes, Hans-Peter"],["dc.contributor.author","Wieland, Thomas"],["dc.date.accessioned","2018-11-07T09:10:09Z"],["dc.date.available","2018-11-07T09:10:09Z"],["dc.date.issued","2012"],["dc.description.abstract","Vascular endothelial growth factor (VEGF) is a main stimulator of pathological vessel formation. Nevertheless, increasing evidence suggests that Angiotensin II (Ang II) can play an augmentory role in this process. We thus analyzed the contribution of the two Ang II receptor types, AT(1)R and AT(2)R, in a mouse model of VEGF-driven angiogenesis, i.e. oxygen-induced proliferative retinopathy. Application of the AT(1)R antagonist telmisartan but not the AT(2)R antagonist PD123,319 largely attenuated the pathological response. A direct effect of Ang II on endothelial cells (EC) was analyzed by assessing angiogenic responses in primary bovine retinal and immortalized rat microvascular EC. Selective stimulation of the AT(1)R by Ang II in the presence of PD123,319 revealed a pro-angiogenic activity which further increased VEGF-driven EC sprouting and migration. In contrast, selective stimulation of the AT(2)R by either CGP42112A or Ang II in the presence of telmisartan inhibited the VEGF-driven angiogenic response. Using specific inhibitors (pertussis toxin, RGS proteins, kinase inhibitors) we identified G(12/13) and G(i) dependent signaling pathways as the mediators of the AT(1)R-induced angiogenesis and the AT(2)R-induced inhibition, respectively. As AT(1)R and AT(2)R stimulation displays opposing effects on the activity of the monomeric GTPase RhoA and pro-angiogenic responses to Ang II and VEGF requires activation of Rho-dependent kinase (ROCK), we conclude that the opposing effects of the Ang II receptors on VEGF-driven angiogenesis converge on the regulation of activity of RhoA-ROCK-dependent EC migration. (c) 2012 Elsevier Inc. All rights reserved."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.1016/j.cellsig.2012.02.005"],["dc.identifier.isi","000303097200017"],["dc.identifier.pmid","22374305"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0898-6568"],["dc.title","Angiotensin H modulates VEGF-driven angiogenesis by opposing effects of type 1 and type 2 receptor stimulation in the microvascular endothelium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","jcs223230"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Cell Science"],["dc.bibliographiccitation.volume","132"],["dc.contributor.author","Leinhos, Lisa"],["dc.contributor.author","Peters, Johannes"],["dc.contributor.author","Krull, Sabine"],["dc.contributor.author","Helbig, Lena"],["dc.contributor.author","Vogler, Melanie"],["dc.contributor.author","Levay, Magdolna"],["dc.contributor.author","van Belle, Gijsbert J."],["dc.contributor.author","Ridley, Anne J."],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Katschinski, Dörthe M."],["dc.contributor.author","Zieseniss, Anke"],["dc.date.accessioned","2020-12-10T18:41:53Z"],["dc.date.available","2020-12-10T18:41:53Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1242/jcs.223230"],["dc.identifier.eissn","1477-9137"],["dc.identifier.issn","0021-9533"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77715"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Hypoxia suppresses myofibroblast differentiation by changing RhoA activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6427"],["dc.bibliographiccitation.journal","International Journal of Nanomedicine"],["dc.bibliographiccitation.lastpage","6428"],["dc.bibliographiccitation.volume","Volume 16"],["dc.contributor.author","Kittana, Naim"],["dc.contributor.author","Assali, Mohyeddin"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Liaw, Norman"],["dc.contributor.author","Santos, Gabriela Leao"],["dc.contributor.author","Rehman, Abdul"],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2022-06-08T07:57:29Z"],["dc.date.available","2022-06-08T07:57:29Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.2147/IJN.S339659"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/110104"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-575"],["dc.relation.eissn","1178-2013"],["dc.title","Modulating the Biomechanical Properties of Engineered Connective Tissues by Chitosan-Coated Multiwall Carbon Nanotubes [Corrigendum]"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","276"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Pharmacology"],["dc.bibliographiccitation.lastpage","16"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Hartmann, Svenja"],["dc.contributor.author","Ridley, Anne J."],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2018-11-07T09:48:49Z"],["dc.date.available","2018-11-07T09:48:49Z"],["dc.date.issued","2015"],["dc.description.abstract","Rho associated kinases ROCK1 and ROCK2 are serine/threonine kinases that are downstream targets of the small GTPases RhoA, RhoB, and RhoC. ROCKs are involved in diverse cellular activities including actin cytoskeleton organization, cell adhesion and motility, proliferation and apoptosis, remodeling of the extracellular matrix and smooth muscle cell contraction. The role of ROCK1 and ROCK2 has long been considered to be similar; however, it is now clear that they do not always have the same functions. Moreover, depending on their subcellular localization, activation, and other environmental factors, ROCK signaling can have different effects on cellular function. With respect to the heart, findings in isoform-specific knockout mice argue for a role of ROCK1 and ROCK2 in the pathogenesis of cardiac fibrosis and cardiac hypertrophy, respectively. Increased ROCK activity could play a pivotal role in processes leading to cardiovascular diseases such as hypertension, pulmonary hypertension, angina pectoris, yasospastic angina, heart failure, and stroke, and thus ROCK activity is a potential new biomarker for heart disease. Pharmacological ROCK inhibition reduces the enhanced ROCK activity in patients, accompanied with a measurable improvement in medical condition. In this review, we focus on recent findings regarding ROCK signaling in the pathogenesis of cardiovascular disease, with a special focus on differences between ROCK1 and ROCK2 function."],["dc.identifier.doi","10.3389/fphar.2015.00276"],["dc.identifier.isi","000366126900001"],["dc.identifier.pmid","26635606"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12684"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35386"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/116"],["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 | C02: RhoGTPasen und ihre Bedeutung für die Last-abhängige Myokardfibrose"],["dc.relation.eissn","1663-9812"],["dc.relation.issn","1663-9812"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The Function of Rho-Associated Kinases ROCK1 and ROCK2 in the Pathogenesis of Cardiovascular Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","overview_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","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","741"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Weber, Pamina"],["dc.contributor.author","Baltus, Doris"],["dc.contributor.author","Jatho, Aline"],["dc.contributor.author","Drews, Oliver"],["dc.contributor.author","Zelarayan, Laura C."],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2021-06-01T09:42:32Z"],["dc.date.available","2021-06-01T09:42:32Z"],["dc.date.issued","2021"],["dc.description.abstract","The Rho guanine nucleotide exchange factor RhoGEF17 was described to reside in adherens junctions (AJ) in endothelial cells (EC) and to play a critical role in the regulation of cell adhesion and barrier function. The purpose of this study was to analyze signal cascades and processes occurring subsequent to AJ disruption induced by RhoGEF17 knockdown. Primary human and immortalized rat EC were used to demonstrate that an adenoviral-mediated knockdown of RhoGEF17 resulted in cell rounding and an impairment in spheroid formation due to an enhanced proteasomal degradation of AJ components. In contrast, β-catenin degradation was impaired, which resulted in an induction of the β-catenin-target genes cyclin D1 and survivin. RhoGEF17 depletion additionally inhibited cell adhesion and sheet migration. The RhoGEF17 knockdown prevented the cells with impeded cell–cell and cell–matrix contacts from apoptosis, which was in line with a reduction in pro-caspase 3 expression and an increase in Akt phosphorylation. Nevertheless, the cells were not able to proliferate as a cell cycle block occurred. In summary, we demonstrate that a loss of RhoGEF17 disturbs cell–cell and cell–substrate interaction in EC. Moreover, it prevents the EC from cell death and blocks cell proliferation. Non-canonical β-catenin signaling and Akt activation could be identified as a potential mechanism."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/cells10040741"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85279"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/391"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C02: RhoGTPasen und ihre Bedeutung für die Last-abhängige Myokardfibrose"],["dc.relation.eissn","2073-4409"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","RhoGEF17—An Essential Regulator of Endothelial Cell Death and Growth"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","31"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","43"],["dc.bibliographiccitation.volume","127"],["dc.contributor.author","Morhenn, Karoline"],["dc.contributor.author","Quentin, Thomas"],["dc.contributor.author","Wichmann, Helen"],["dc.contributor.author","Steinmetz, Michael"],["dc.contributor.author","Prondzynski, Maksymilian"],["dc.contributor.author","Söhren, Klaus-Dieter"],["dc.contributor.author","Christ, Torsten"],["dc.contributor.author","Geertz, Birgit"],["dc.contributor.author","Schröder, Sabine"],["dc.contributor.author","Schöndube, Friedrich A."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Schlossarek, Saskia"],["dc.contributor.author","Zimmermann, Wolfram H."],["dc.contributor.author","Carrier, Lucie"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Cardinaux, Jean-René"],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Oetjen, Elke"],["dc.date.accessioned","2020-12-10T15:21:48Z"],["dc.date.available","2020-12-10T15:21:48Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.yjmcc.2018.12.001"],["dc.identifier.issn","0022-2828"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73167"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Mechanistic role of the CREB-regulated transcription coactivator 1 in cardiac hypertrophy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0137519"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Jatho, Aline"],["dc.contributor.author","Hartmann, Svenja"],["dc.contributor.author","Kittana, Naim"],["dc.contributor.author","Muegge, Felicitas"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Katschinski, Dörthe M."],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2017-09-07T11:43:28Z"],["dc.date.available","2017-09-07T11:43:28Z"],["dc.date.issued","2015"],["dc.description.abstract","Introduction RhoA has been shown to be beneficial in cardiac disease models when overexpressed in cardiomyocytes, whereas its role in cardiac fibroblasts (CF) is still poorly understood. During cardiac remodeling CF undergo a transition towards a myofibroblast phenotype thereby showing an increased proliferation and migration rate. Both processes involve the remodeling of the cytoskeleton. Since RhoA is known to be a major regulator of the cytoskeleton, we analyzed its role in CF and its effect on myofibroblast characteristics in 2 D and 3D models. Results Downregulation of RhoA was shown to strongly affect the actin cytoskeleton. It decreased the myofibroblast marker alpha-sm-actin, but increased certain fibrosis-associated factors like TGF-beta and collagens. Also, the detailed analysis of CTGF expression demonstrated that the outcome of RhoA signaling strongly depends on the involved stimulus. Furthermore, we show that proliferation of myofibroblasts rely on RhoA and tubulin acetylation. In assays accessing three different types of migration, we demonstrate that RhoA/ROCK/Dia1 are important for 2D migration and the repression of RhoA and Dia1 signaling accelerates 3D migration. Finally, we show that a downregulation of RhoA in CF impacts the viscoelastic and contractile properties of engineered tissues. Conclusion RhoA positively and negatively influences myofibroblast characteristics by differential signaling cascades and depending on environmental conditions. These include gene expression, migration and proliferation. Reduction of RhoA leads to an increased viscoelasticity and a decrease in contractile force in engineered cardiac tissue."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.1371/journal.pone.0137519"],["dc.identifier.gro","3141809"],["dc.identifier.isi","000362511000003"],["dc.identifier.pmid","26448568"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12214"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1312"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/118"],["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 | 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","SFB 1002 | C06: Mechanismen und Regulation der koronaren Gefäßneubildung"],["dc.relation.issn","1932-6203"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","RhoA Ambivalently Controls Prominent Myofibroblast Characteritics by Involving Distinct Signaling Routes"],["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.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","39"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","54"],["dc.bibliographiccitation.volume","88"],["dc.contributor.author","Ongherth, Anita"],["dc.contributor.author","Pasch, Sebastian"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","Nowak, Karolin"],["dc.contributor.author","Kittana, Naim"],["dc.contributor.author","Weis, Cleo A."],["dc.contributor.author","Jatho, Aline"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2017-09-07T11:43:27Z"],["dc.date.available","2017-09-07T11:43:27Z"],["dc.date.issued","2015"],["dc.description.abstract","Cardiac remodeling, a hallmark of heart disease, is associated with intense auto- and paracrine signaling leading to cardiac fibrosis. We hypothesized that the specific mediator of G(q/11)-dependent RhoA activation p63RhoGEF, which is expressed in cardiac fibroblasts, plays a role in the underlying processes. We could show that p63RhoGEF is up-regulated in mouse hearts subjected to transverse aortic constriction (TAC). In an engineered heart muscle model (EHM), p63RhoGEF expression in cardiac fibroblasts increased resting and twitch tensions, and the dominant negative p63 Delta N decreased both. In an engineered connective tissue model (ECT), p63RhoGEF increased tissue stiffness and its knockdown as well as p63 Delta N reduced stiffness. In 2D cultures of neonatal rat cardiac fibroblasts, p63RhoGEF regulated the angiotensin II (Ang II)-dependent RhoA activation, the activation of the serum response factor, and the expression and secretion of the connective tissue growth factor (CTGF). All these processes were inhibited by the knockdown of p63RhoGEF or by p63 Delta N likely based on their negative influence on the actin cytoskeleton. Moreover, we show that p63RhoGEF also regulates CTGF in engineered tissues and correlates with it in the TAC model. Finally, confocal studies revealed a closely related localization of p63RhoGEF and CTGF in the trans-Golgi network. (C) 2015 Published by Elsevier Ltd."],["dc.identifier.doi","10.1016/j.yjmcc.2015.09.009"],["dc.identifier.gro","3141795"],["dc.identifier.isi","000365059300004"],["dc.identifier.pmid","26392029"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1157"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/117"],["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 | 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","1095-8584"],["dc.relation.issn","0022-2828"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.title","p63RhoGEF regulates auto- and paracrine signaling in cardiac fibroblasts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]