El-Armouche, Ali

[["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","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"]]

[["dc.bibliographiccitation.firstpage","97"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","107"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Kaul, Axel"],["dc.contributor.author","Sbroggi, Mauro"],["dc.contributor.author","Schubert, Carola"],["dc.contributor.author","Regitz-Zagrosek, Vera"],["dc.contributor.author","Brancaccio, Mara"],["dc.contributor.author","Damilano, Federico"],["dc.contributor.author","Hirsch, Emilio"],["dc.contributor.author","Bilsen, Marc van"],["dc.contributor.author","Munts, Chantal"],["dc.contributor.author","Sipido, Karin"],["dc.contributor.author","Bito, Virginie"],["dc.contributor.author","Detre, Elke"],["dc.contributor.author","Wagner, Nana Maria"],["dc.contributor.author","Schaefer, Katrin"],["dc.contributor.author","Seidler, Tim"],["dc.contributor.author","Vogt, Johannes"],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Balligand, Jean Luc"],["dc.contributor.author","Bouzin, Caroline"],["dc.contributor.author","Ventura-Clapier, Renee"],["dc.contributor.author","Garnier, Anne"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Knoell, Ralph"],["dc.contributor.author","Tarone, Guido"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.date.accessioned","2017-09-07T11:46:57Z"],["dc.date.available","2017-09-07T11:46:57Z"],["dc.date.issued","2014"],["dc.description.abstract","Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach. Mice overexpressing melusin in the heart (TG) and wild-type controls (WT) were subjected to permanent LAD ligation and both the acute response (Day 3) and subsequent remodelling (2 weeks) were examined. Mortality in wild-type mice was significant between Days 3 and 7, primarily due to cardiac rupture, but melusins overexpression strongly reduced mortality (43.2 in wild-type vs. 27.3 in melusin-TG, P 0.005). At Day 3 after MI, a time point preceding the mortality peak, TG hearts had increased heat shock protein 70 expression, increased ERK1/2 signalling, reduced cardiomyocyte hyper-contractility and inflammatory cell infiltrates, and increased matricellular protein expression in the infarcted area. At 2 weeks after MI, melusin overexpression conferred a favourable adaptive remodelling characterized by reduced left ventricle dilatation and better preserved contractility in the presence of a comparable degree of hypertrophy. Adaptive remodelling in melusin TG mice was characterized by reduced apoptosis and fibrosis as well as increased cardiomyocyte contractility. Consistent with its function as a chaperone protein, melusin overexpression exerts a dual protective action following MI reducing an array of maladaptive processes. In the early phase after MI, reduced inflammation and myocyte remodelling protect against cardiac rupture. Chronically, reduced myocyte loss and matrix remodelling, with preserved myocyte contractility, confer adaptive LV remodelling."],["dc.identifier.doi","10.1093/cvr/cvt235"],["dc.identifier.gro","3142225"],["dc.identifier.isi","000329043200013"],["dc.identifier.pmid","24130190"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5921"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: EU [LSHM-CT-2005-018833]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1755-3245"],["dc.relation.issn","0008-6363"],["dc.title","Melusin protects from cardiac rupture and improves functional remodelling after myocardial infarction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","617"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","626"],["dc.bibliographiccitation.volume","120"],["dc.contributor.author","Wittoepper, Katrin"],["dc.contributor.author","Fabritz, Larissa"],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Ort, Katharina R."],["dc.contributor.author","Grefe, Clemens"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Kirchhof, Paulus"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Dobrev, Dobromir"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2017-09-07T11:46:09Z"],["dc.date.available","2017-09-07T11:46:09Z"],["dc.date.issued","2010"],["dc.description.abstract","Phosphatase inhibitor-1 (I-1) is a distal amplifier element of P-adrenergic signaling that functions by preventing dephosphorylation of downstream targets. I-1 is downregulated in human failing hearts, while overexpression of a constitutively active mutant form (I-1c) reverses contractile dysfunction in mouse failing hearts, suggesting that I-1c may be a candidate for gene therapy. We generated mice with conditional cardiomyocyte-restricted expression of I-1c (referred to herein as dTG(I-1c) mice) on an I-1-deficient background. Young adult dTG(I-1c) mice exhibited enhanced cardiac contractility but exaggerated contractile dysfunction and ventricular dilation upon catecholamine infusion. Telemetric ECG recordings revealed typical catecholamine-induced ventricular tachycardia and sudden death. Doxycycline feeding switched off expression of cardiomyocyte-restricted I-1c and reversed all abnormalities. Hearts from dTG(I-1c) mice showed hyperphosphorylation of phospholamban and the ryanodine receptor, and this was associated with an increased number of catecholamine-induced Ca(2+) sparks in isolated myocytes. Aged dTG(I-1c) mice spontaneously developed a cardiomyopathic phenotype. These data were confirmed in a second independent transgenic mouse line, expressing a full-length I-I mutant that could not be phosphorylated and thereby inactivated by PKC-alpha (I-1(S67A)). In conclusion, conditional expression of I-1c or I-1(S67A) enhanced steady-state phosphorylation of 2 key Ca(2+)-regulating sarcoplasmic reticulum enzymes. This was associated with increased contractile function in young animals but also with arrhythmias and cardiomyopathy after adrenergic stress and with aging. These data should be considered in the development of novel therapies for heart failure."],["dc.identifier.doi","10.1172/JCI40545"],["dc.identifier.gro","3142974"],["dc.identifier.isi","000274040000020"],["dc.identifier.pmid","20071777"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6149"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/437"],["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","Amer Soc Clinical Investigation Inc"],["dc.relation.issn","0021-9738"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging"],["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.firstpage","621"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Circulation Heart Failure"],["dc.bibliographiccitation.lastpage","627"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Ouchi, Noriyuki"],["dc.contributor.author","Tanaka, Komei"],["dc.contributor.author","Doros, Gheorghe"],["dc.contributor.author","Wittkoepper, Katrin"],["dc.contributor.author","Schulze, Thomas"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Walsh, Kenneth"],["dc.contributor.author","Sam, Flora"],["dc.date.accessioned","2018-11-07T08:52:26Z"],["dc.date.available","2018-11-07T08:52:26Z"],["dc.date.issued","2011"],["dc.description.abstract","Background-Follistatin-like 1 (FSTL1) is an extracellular glycoprotein found in human serum. Recent work suggests that FSTL1 is secreted in response to ischemic injuries and that its overexpression is protective in the heart and vasculature. Methods and Results-We examined serum FSTL1 levels in patients with chronic heart failure with left ventricular (LV) ejection fraction <40% (n=86). The sample was separated into three tertiles of patients with low, medium, and high FSTL1 levels. Serum FSTL1 was increased 56% above age-and sex-matched healthy controls. Diabetes mellitus, brain natriuretic peptide level, left atrial size, LV posterior wall thickness, LV end-diastolic diameter, and LV mass were significant determinants of FSTL1 serum levels by bivariate analysis. After controlling for significant covariates, FSTL1 levels predicted LV hypertrophy (as measured by LV mass index) by multivariate linear regression analysis (P<0.001). Unadjusted survival analysis demonstrated increased mortality in patients with increasing FSTL1 levels (P=0.09). After adjusting for significant parameters, patients with increased FSTL1 remained at the highest risk of death (hazard ratio, 1.028; 95% CI, 0.98 to 1.78; P=0.26). To determine whether elevated FSTL1 levels may be derived from the myocardium, FSTL1 protein expression was measured in explanted failing (n=18) and nonfailing (n=7) human hearts. LV failing hearts showed 2.5-fold higher FSTL1 protein levels over nonfailing control hearts (P<.05). Conclusions-Elevated serum FSTL1 in patients with heart failure was associated with LV hypertrophy. Further studies on the role of FSTL1 as a biomarker in chronic systolic heart failure are warranted. (Circ Heart Fail. 2011;4:621-627.)"],["dc.description.sponsorship","National Heart, Lung, and Blood Institute [HL102631, HL079099]"],["dc.identifier.doi","10.1161/CIRCHEARTFAILURE.110.960625"],["dc.identifier.isi","000295035000015"],["dc.identifier.pmid","21622850"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8227"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22163"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1941-3289"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Follistatin-Like 1 in Chronic Systolic Heart Failure A Marker of Left Ventricular Remodeling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","H907"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","American Journal of Physiology - Heart and Circulatory Physiology"],["dc.bibliographiccitation.lastpage","H914"],["dc.bibliographiccitation.volume","285"],["dc.contributor.author","Wiechert, S"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Rau, T."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.date.accessioned","2017-09-07T11:44:18Z"],["dc.date.available","2017-09-07T11:44:18Z"],["dc.date.issued","2003"],["dc.description.abstract","The human genome project has increased the demand for simple experimental systems that allow the impact of gene manipulations to be studied under controlled ex vivo conditions. We hypothesized that, in contrast to adult hearts, neonatal hearts allow long-term perfusion and efficient gene transfer ex vivo. A Langendorff perfusion system was modified to allow perfusion for >24 h with particular emphasis on uncompromised contractile activity, sterility, online measurement of force of contraction, inotropic response to beta-adrenergic stimulation, and efficient gene transfer. The hearts were perfused with serum-free medium (DMEM + medium 199, 4 + 1) supplemented with hydrocortisone, triiodothyronine, ascorbic acid, insulin, pyruvate, L-carnitine, creatine, taurine, L-glutamine, mannitol, and antibiotics recirculating (500 ml/2 hearts) at 1 ml/min. Hearts from 2 day-old rats beat constantly at 135-155 beats/min and developed active force of 1-2 mN. During 24 h of perfusion, twitch tension increased to similar to165% of initial values (P < 0.05), whereas the inotropic response to isoprenaline remained constant. A decrease in total protein content of 10% and histological examination indicated moderate edema, but actin and calsequestrin concentration remained unchanged and perfusion pressure remained constant at 7-11 mmHg. Perfusion with a LacZ-encoding adenovirus at 3 x 10(8) active virus particles yielded homogeneous transfection of &SIM;80% throughout the heart and did not affect heart rate, force of contraction, or response to isoprenaline compared with uninfected controls (n = 7 each). Taken together, the 24-h Langendorff-perfused neonatal rat heart is a relatively simple, inexpensive, and robust new heart model that appears feasible as a test bed for functional genomics."],["dc.identifier.doi","10.1152/ajpheart.00856.2002"],["dc.identifier.gro","3144073"],["dc.identifier.isi","000184153100054"],["dc.identifier.pmid","12663262"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1657"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0363-6135"],["dc.title","24-h Langendorff-perfused neonatal rat heart used to study the impact of adenoviral gene transfer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The Journal of Heart and Lung Transplantation"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Schwoerer, A. P."],["dc.contributor.author","Biermann, D."],["dc.contributor.author","Boknik, Peter"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Volk, T."],["dc.contributor.author","Reichenspurner, Hermann"],["dc.contributor.author","Ehmke, H."],["dc.date.accessioned","2018-11-07T09:41:52Z"],["dc.date.available","2018-11-07T09:41:52Z"],["dc.date.issued","2014"],["dc.format.extent","S234"],["dc.identifier.isi","000333866700633"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33828"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.publisher.place","New york"],["dc.relation.conference","34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation"],["dc.relation.eventlocation","San Diego, CA"],["dc.relation.issn","1557-3117"],["dc.relation.issn","1053-2498"],["dc.title","Cellular Ca2+Handling in Cardiac Atrophy and Hypertrophy"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e98893"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Neuber, Christiane"],["dc.contributor.author","Uebeler, June"],["dc.contributor.author","Schulze, Thomas"],["dc.contributor.author","Sotoud, Hannieh"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.date.accessioned","2018-11-07T09:39:00Z"],["dc.date.available","2018-11-07T09:39:00Z"],["dc.date.issued","2014"],["dc.description.abstract","Endoplasmic reticulum (ER) stress has been implicated in a variety of cardiovascular diseases. During ER stress, disruption of the complex of protein phosphatase 1 regulatory subunit 15A and catalytic subunit of protein phosphatase 1 by the small molecule guanabenz (antihypertensive, alpha(2)-adrenoceptor agonist) and subsequent inhibition of stress-induced dephosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) results in prolonged eIF2 alpha phosphorylation, inhibition of protein synthesis and protection from ER stress. In this study we assessed whether guanabenz protects against ER stress in cardiac myocytes and affects the function of 3 dimensional engineered heart tissue (EHT). We utilized neonatal rat cardiac myocytes for the assessment of cell viability and activation of ER stress-signalling pathways and EHT for functional analysis. (i) Tunicamycin induced ER stress as measured by increased mRNA and protein levels of glucose-regulated protein 78 kDa, P-eIF2 alpha, activating transcription factor 4, C/EBP homologous protein, and cell death. (ii) Guanabenz had no measurable effect alone, but antagonized the effects of tunicamycin on ER stress markers. (iii) Tunicamycin and other known inducers of ER stress (hydrogen peroxide, doxorubicin, thapsigargin) induced cardiac myocyte death, and this was antagonized by guanabenz in a concentration-and time-dependent manner. (iv) ER stressors also induced acute or delayed contractile dysfunction in spontaneously beating EHTs and this was, with the notable exception of relaxation deficits under thapsigargin, not significantly affected by guanabenz. The data confirm that guanabenz interferes with ER stress-signalling and has protective effects on cell survival. Data show for the first time that this concept extends to cardiac myocytes. The modest protection in EHTs points to more complex mechanisms of force regulation in intact functional heart muscle."],["dc.description.sponsorship","European Union"],["dc.identifier.doi","10.1371/journal.pone.0098893"],["dc.identifier.isi","000336911400107"],["dc.identifier.pmid","24892553"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10495"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33186"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Guanabenz Interferes with ER Stress and Exerts Protective Effects in Cardiac Myocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]