Zimmermann, Wolfram-Hubertus

[["dc.bibliographiccitation.firstpage","47"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Ultrasound in Medicine & Biology"],["dc.bibliographiccitation.lastpage","55"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Wasmeier, Gerald H."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Schineis, Nico"],["dc.contributor.author","Melnychenko, Ivan"],["dc.contributor.author","Voigt, Jens-Uwe"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Flachskampf, Frank A."],["dc.contributor.author","Daniel, Werner G."],["dc.contributor.author","Nixdorff, Uwe"],["dc.date.accessioned","2017-09-07T11:48:49Z"],["dc.date.available","2017-09-07T11:48:49Z"],["dc.date.issued","2008"],["dc.description.abstract","Real-time myocardial contrast echocardiography (MCE) is a noninvasive perfusion imaging method, whereas technical and resolution problems impair its application in small animals. Hence, we investigated the feasibility of NICE in experimental cardiovascular set-ups involving healthy and infarcted myocardium in rats. Twenty-five male Wistar rats were examined under volatile anesthesia (2.5% isoflurane) with high-resolution conventional 2-D echocardiography (2DE) and real-time MICE (Sonos 7500 with 15MHz-transducer, Philips Medical Systems, Andover, MA, USA) in short-axis view. Contrast agent (SonoVue, Bracco, Milan, Italy) was infused as a bolus into a sublingual vein. Background-subtracted contrast signal intensity (SI) was measured off-line in six end-systolic segments and fitted to an exponential curve (gamma variate). Derived peak SI was subsequently calculated and compared with wall motion and common functional measured quantities (left ventricular end-diastolic diameter [LVEDD], area shortening [AS]). Recordings were performed before and 14 days after left anterior descending (LAD) ligature. Infarction induced anterior wall motion abnormalities (WMA) in all animals (16 akinetic, 9 hypokinetic), increased LVEDD (9.1 +/- 0.6 vs. 7.9 +/- 0.6 mm, p < 0.001), reduced AS (36.1 +/- 10.0 vs. 59.5 +/- 4.1%, p < 0.001) and reduced anterior segmental SI (0.4 +/- 0.4 dB akinetic / 1.7 +/- 1.7 dB hypokinetic vs. 15.8 +/- 10.9 dB preinfarct, p < 0.001 / p < 0.001). Segmental SI in normokinetic segments remained unchanged. Area at risk (perfusion defect) correlated well with WMA (r = 0.838). These data confirmed high-resolution real-time NICE as a rational tool for assessing myocardial perfusion of Wistar rats. It may therefore be a useful diagnostic tool for ill-vivo cardiovascular research in small animals."],["dc.identifier.doi","10.1016/j.ultrasmedbio.2007.06.027"],["dc.identifier.gro","3143391"],["dc.identifier.isi","000252038900007"],["dc.identifier.pmid","17854980"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/899"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0301-5629"],["dc.title","Real-time myocardial contrast echocardiography for assessing perfusion and function in healthy and infarcted Wistar rats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","ehy600"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.lastpage","19"],["dc.contributor.author","Maack, Christoph"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Hamdani, Nazha"],["dc.contributor.author","Heinzel, Frank R."],["dc.contributor.author","Lyon, Alexander R."],["dc.contributor.author","Manstein, Dietmar J."],["dc.contributor.author","Metzger, Joseph"],["dc.contributor.author","Papp, Zoltán"],["dc.contributor.author","Tocchetti, Carlo G."],["dc.contributor.author","Yilmaz, M. Birhan"],["dc.contributor.author","Anker, Stefan D."],["dc.contributor.author","Balligand, Jean-Luc"],["dc.contributor.author","Bauersachs, Johann"],["dc.contributor.author","Brutsaert, Dirk"],["dc.contributor.author","Carrier, Lucie"],["dc.contributor.author","Chlopicki, Stefan"],["dc.contributor.author","Cleland, John G."],["dc.contributor.author","de Boer, Rudolf A."],["dc.contributor.author","Dietl, Alexander"],["dc.contributor.author","Fischmeister, Rodolphe"],["dc.contributor.author","Harjola, Veli-Pekka"],["dc.contributor.author","Heymans, Stephane"],["dc.contributor.author","Hilfiker-Kleiner, Denise"],["dc.contributor.author","Holzmeister, Johannes"],["dc.contributor.author","de Keulenaer, Gilles"],["dc.contributor.author","Limongelli, Giuseppe"],["dc.contributor.author","Linke, Wolfgang A."],["dc.contributor.author","Lund, Lars H."],["dc.contributor.author","Masip, Josep"],["dc.contributor.author","Metra, Marco"],["dc.contributor.author","Mueller, Christian"],["dc.contributor.author","Pieske, Burkert"],["dc.contributor.author","Ponikowski, Piotr"],["dc.contributor.author","Ristić, Arsen"],["dc.contributor.author","Ruschitzka, Frank"],["dc.contributor.author","Seferović, Petar M."],["dc.contributor.author","Skouri, Hadi"],["dc.contributor.author","Zimmermann, Wolfram H."],["dc.contributor.author","Mebazaa, Alexandre"],["dc.date.accessioned","2019-02-20T13:50:51Z"],["dc.date.available","2019-02-20T13:50:51Z"],["dc.date.issued","2018"],["dc.description.abstract","Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation–contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term."],["dc.identifier.doi","10.1093/eurheartj/ehy600"],["dc.identifier.pmid","30295807"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57605"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/235"],["dc.language.iso","en"],["dc.notes.status","fcwi"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C01: Epigenetische Kontrolle der Herzfibrose"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation.workinggroup","RG Linke (Kardiovaskuläre Physiologie)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.title","Treatments targeting inotropy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","909"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Hepatology"],["dc.bibliographiccitation.lastpage","918"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Sass, Gabriele"],["dc.contributor.author","Soares, Miguel Che Parreira"],["dc.contributor.author","Yamashita, Kenichiro"],["dc.contributor.author","Seyfried, Stefan"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Kaczmarek, Elzbieta"],["dc.contributor.author","Ritter, Thomas"],["dc.contributor.author","Volk, Hans-Dieter"],["dc.contributor.author","Tiegs, Gisa"],["dc.date.accessioned","2017-09-07T11:54:28Z"],["dc.date.available","2017-09-07T11:54:28Z"],["dc.date.issued","2003"],["dc.description.abstract","Heme oxygenase‐1 (HO‐1), a stress‐responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin, and iron, has previously been shown to protect grafts from ischemia/reperfusion injury and rejection. Here we investigated the protective potential of HO‐1 in 5 models of immune‐mediated liver injury. We found that up‐regulation of endogenous HO‐1 by cobalt‐protoporphyrin‐IX (CoPP) protected mice from apoptotic liver damage induced by anti‐CD95 antibody (Ab) or D‐galactosamine in combination with either anti‐CD3 Ab, lipopolysaccharide (LPS), or tumor necrosis factor α (TNF‐α). HO‐1 induction prevented apoptotic liver injury, measured by inhibition of caspase 3 activation, although it did not protect mice from caspase‐3—independent necrotic liver damage caused by concanavalin A (Con A) administration. In addition, overexpression of HO‐1 by adenoviral gene transfer resulted in protection from apoptotic liver injury, whereas inhibition of HO‐1 enzymatic activity by tin‐protoporphyrin‐IX (SnPP) abrogated the protective effect. HO‐1—mediated protection seems to target parenchymal liver cells directly because CoPP treatment protected isolated primary hepatocytes from anti‐CD95—induced apoptosis in vitro. Furthermore, depletion of Kupffer cells (KCs) did not interfere with the protective effect in vivo. Exogenous CO administration or treatment with the CO‐releasing agent methylene chloride mimicked the protective effect of HO‐1, whereas treatment with exogenous biliverdin or overexpression of ferritin by recombinant adenoviral gene transfer did not. In conclusion, HO‐1 is a potent protective factor for cytokine‐ and CD95‐mediated apoptotic liver damage. Induction of HO‐1 might be of a therapeutic modality for inflammatory liver diseases."],["dc.identifier.doi","10.1002/hep.1840380417"],["dc.identifier.gro","3145182"],["dc.identifier.pii","S0270-9139(03)00677-3"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2889"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0270-9139"],["dc.title","Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.peerReviewed","no"],["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.firstpage","452"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","458"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Melnychenko, Ivan"],["dc.contributor.author","Wasmeier, Gerald H."],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Naito, Hiroshi"],["dc.contributor.author","Nixdorff, U"],["dc.contributor.author","Hess, Andreas"],["dc.contributor.author","Budinsky, L."],["dc.contributor.author","Brune, K"],["dc.contributor.author","Michaelis, B."],["dc.contributor.author","Dhein, S."],["dc.contributor.author","Schwoerer, Alexander Peter"],["dc.contributor.author","Ehmke, Heimo"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.date.accessioned","2017-09-07T11:53:08Z"],["dc.date.available","2017-09-07T11:53:08Z"],["dc.date.issued","2006"],["dc.description.abstract","The concept of regenerating diseased myocardium by implantation of tissue-engineered heart muscle is intriguing, but convincing evidence is lacking that heart tissues can be generated at a size and with contractile properties that would lend considerable support to failing hearts. Here we created large (thickness/ diameter, 1-4 mm/15 mm), force-generating engineered heart tissue from neonatal rat heart cells. Engineered heart tissue formed thick cardiac muscle layers when implanted on myocardial infarcts in immune-suppressed rats. When evaluated 28 d later, engineered heart tissue showed undelayed electrical coupling to the native myocardium without evidence of arrhythmia induction. Moreover, engineered heart tissue prevented further dilation, induced systolic wall thickening of infarcted myocardial segments and improved fractional area shortening of infarcted hearts compared to controls (sham operation and noncontractile constructs). Thus, our study provides evidence that large contractile cardiac tissue grafts can be constructed in vitro, can survive after implantation and can support contractile function of infarcted hearts."],["dc.identifier.doi","10.1038/nm1394"],["dc.identifier.gro","3143714"],["dc.identifier.isi","000236581300035"],["dc.identifier.pmid","16582915"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1259"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1078-8956"],["dc.title","Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","435"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Future Cardiology"],["dc.bibliographiccitation.lastpage","445"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.date.accessioned","2017-09-07T11:54:28Z"],["dc.date.available","2017-09-07T11:54:28Z"],["dc.date.issued","2011"],["dc.description.abstract","Engineered myocardium may be used to repair myocardial defects. Although not clinically applicable yet, initial studies in rodents have demonstrated the feasibility of tissue engineering based myocardial repair in vivo. In order for restorative treatment to evolve into a functional treatment modality, tissue engineers have to generate human myocardium of sufficient size and with relevant contractile function to replace/repair myocardial defects. This requires the identification of a scalable and ideally autologous cardiomyocyte source as well as the development of strategies to overcome size limitations. We will further address pivotal issues pertaining to the allocation of suitable human cells for myocardial tissue engineering and discuss the translation of present myocardial tissue engineering concepts into preclinical, as well as clinical, trials."],["dc.identifier.doi","10.2217/14796678.3.4.435"],["dc.identifier.gro","3145184"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2892"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","1479-6678"],["dc.title","Cardiac tissue engineering: a clinical perspective"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S247"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.lastpage","S254"],["dc.bibliographiccitation.volume","120"],["dc.contributor.author","Deuse, Tobias"],["dc.contributor.author","Peter, Christoph"],["dc.contributor.author","Fedak, Paul W. M."],["dc.contributor.author","Doyle, Tim"],["dc.contributor.author","Reichenspurner, Hermann"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Stein, William"],["dc.contributor.author","Wu, Joseph C."],["dc.contributor.author","Robbins, Robert C."],["dc.contributor.author","Schrepfer, Sonja"],["dc.date.accessioned","2017-09-07T11:46:49Z"],["dc.date.available","2017-09-07T11:46:49Z"],["dc.date.issued","2009"],["dc.description.abstract","Background-Mesenchymal stem cell (MSC)-based regenerative strategies were investigated to treat acute myocardial infarction and improve left ventricular function. Methods and Results-Murine AMI was induced by coronary ligation with subsequent injection of MSCs, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), or MSCs +HGF/VEGF into the border zone. Left ventricular ejection fraction was calculated using micro-computed tomography imaging after 6 months. HGF and VEGF protein injection (with or without concomitant MSC injection) significantly and similarly improved the left ventricular ejection fraction and reduced scar size compared with the MSC group, suggesting that myocardial recovery was due to the cytokines rather than myocardial regeneration. To provide sustained paracrine effects, HGF or VEGF overexpressing MSCs were generated (MSC-HGF, MSC-VEGF). MSC-HGF and MSC-VEGF showed significantly increased in vitro proliferation and increased in vivo proliferation within the border zone. Cytokine production correlated with MSC survival. MSC-HGF-and MSC-VEGF-treated animals showed smaller scar sizes, increased peri-infarct vessel densities, and better preserved left ventricular function when compared with MSCs transfected with empty vector. Murine cardiomyocytes were exposed to hypoxic in vitro conditions. The LDH release was reduced, fewer cardiomyocytes were apoptotic, and Akt activity was increased if cardiomyocytes were maintained in conditioned medium obtained from MSC-HGF or MSC-VEGF cultures. Conclusions-This study showed that (1) elevating the tissue levels of HGF and VEGF after acute myocardial infarction seems to be a promising reparative therapeutic approach, (2) HGF and VEGF are cardioprotective by increasing the tolerance of cardiomyocytes to ischemia, reducing cardiomyocyte apoptosis and increasing prosurvival Akt activation, and (3) MSC-HGF and MSC-VEGF are a valuable source for increased cytokine production and maximize the beneficial effect of MSC-based repair strategies. (Circulation. 2009; 120[suppl 1]: S247-S254.)"],["dc.identifier.doi","10.1161/CIRCULATIONAHA.108.843680"],["dc.identifier.gro","3143055"],["dc.identifier.isi","000269773000035"],["dc.identifier.pmid","19752375"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/527"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","81st Annual Scientific Session of the American-Heart-Association"],["dc.relation.eventlocation","New Orleans, LA"],["dc.relation.ispartof","Circulation"],["dc.relation.issn","0009-7322"],["dc.title","Hepatocyte Growth Factor or Vascular Endothelial Growth Factor Gene Transfer Maximizes Mesenchymal Stem Cell-Based Myocardial Salvage After Acute Myocardial Infarction"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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","156"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Interactive CardioVascular and Thoracic Surgery"],["dc.bibliographiccitation.lastpage","161"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Naito, Hiroshi"],["dc.contributor.author","Tojo, Takashi"],["dc.contributor.author","Kimura, Michitaka"],["dc.contributor.author","Dohi, Yoshiko"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Taniguchi, Shigeki"],["dc.date.accessioned","2017-09-07T11:44:23Z"],["dc.date.available","2017-09-07T11:44:23Z"],["dc.date.issued","2011"],["dc.description.abstract","We aimed at providing the first in vitro and in vivo proof-of-concept for a novel tracheal tissue engineering technology. We hypothesized that bioartificial trachea (BT) could be generated from fibroblast and collagen hydrogels, mechanically supported by osteogenically-induced mesenchymal stem cells (MSC) in ring-shaped 3D-hydrogel cultures, and applied in an experimental model of rat trachea injury. Tube-shaped tissue was constructed from mixtures of rat fibroblasts and collagen in custom-made casting molds. The tissue was characterized histologically and mechanically. Ring-shaped tissue was constructed from mixtures of rat MSCs and collagen and fused to the tissue-engineered tubes to function as reinforcement. Stiffness of the biological reinforcement was enhanced by induction of osteogeneic differentiation in MSCs. Osteogenic differentiation was evaluated by assessment of osteocalcin (OC) secretion, quantification of calcium (Ca) deposit, and mechanical testing. Finally, BT was implanted to bridge a surgically-induced tracheal defect. A three-layer tubular tissue structure composed of an interconnected network of fibroblasts was constructed. Tissue collapse was prevented by the placement of MSC-containing ring-shaped tissue reinforcement around the tubular constructs. Osteogenic induction resulted in high OC secretion, high Ca deposit, and enhanced construct stiffness. Ultimately, when BT was implanted, recipient rats were able to breathe spontaneously. (C) 2011 Published by European Association for Cardio-Thoracic Surgery. All rights reserved."],["dc.identifier.doi","10.1510/icvts.2010.253559"],["dc.identifier.gro","3142782"],["dc.identifier.isi","000309930500019"],["dc.identifier.pmid","21098511"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/223"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1569-9293"],["dc.title","Engineering bioartificial tracheal tissue using hybrid fibroblast-mesenchymal stem cell cultures in collagen hydrogels"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","211"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","220"],["dc.bibliographiccitation.volume","65"],["dc.contributor.author","Grimm, Michael"],["dc.contributor.author","Haas, P."],["dc.contributor.author","Willipinski-Stapelfeldt, B"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Rau, T."],["dc.contributor.author","Pantel, K ."],["dc.contributor.author","Weyand, M"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.date.accessioned","2017-09-07T11:43:03Z"],["dc.date.available","2017-09-07T11:43:03Z"],["dc.date.issued","2005"],["dc.description.abstract","Objective: Mechanisms of the positive inotropic response to alpha(1)-adrenergic stimulation in the heart remain poorly understood, but recent evidence in rat papillary muscle suggests an important role of regulatory myosin light chain (MLC2) phosphorylation. This study investigated alpha(1)-adrenergic contractile effects and the role of MLC kinase (MLCK)-dependent phosphorylation of MLC2 in human atrial muscle strips. Methods: Force measurement was performed on electrically stimulated atrial muscle strips (n = 140; 20 hearts) in the presence of the betablocker nadolol. MLC2a phosphorylation was determined by 2D-polyacrylamide gel electrophoresis and Western blotting of muscle strips that were immediately freeze-clamped following force measurements. Results: The alpha(1)-agonist phenylephrine (PE; 0.3-100 muM) exerted a concentration-dependent, monophasic, sustained positive inotropic effect (86% above basal) that was accompanied by an 80% increase in MLC2a phosphorylation. Desinhibition of MLC phosphatase by the Rho kinase inhibitor Y-27632 (10 muM) reduced the effect of PE by 16%. The MLCK inhibitor wortmannin (10 muM) completely abolished both the PE-induced increase in force and MLC2a phosphorylation. The structurally unrelated MLCK inhibitor ML-7 (10 muM) had similar effects. Neither Y-27632 nor wortmannin or ML-7 affected beta-adrenergic force stimulation. In contrast to our findings in atrial muscle strips, we observed no increase in MLC2v phosphorylation after PE in human ventricular muscle strips and wortmannin failed to inhibit PE-induced force of contraction. Conclusion: alpha(1)-Adrenergic receptors mediate a prominent increase in contractile force in human atria that depends on MLCK activity and is accompanied by an increase in MLC2 phosphorylation. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.cardiores.2004.09.019"],["dc.identifier.gro","3143910"],["dc.identifier.isi","000226477600025"],["dc.identifier.pmid","15621049"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1476"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0008-6363"],["dc.title","Key role of myosin light chain (MLC) kinase-mediated MLC2a phosphorylation in the alpha(1)-adrenergic positive inotropic effect in human atrium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]