Eschenhagen, Thomas

[["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","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","642"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","651"],["dc.bibliographiccitation.volume","79"],["dc.contributor.author","Kockskaemper, Jens"],["dc.contributor.author","Khafaga, Mounir"],["dc.contributor.author","Grimm, Michael"],["dc.contributor.author","Elgner, Andreas"],["dc.contributor.author","Walther, Stefanie"],["dc.contributor.author","Kockskaemper, Anke"],["dc.contributor.author","von Lewinski, Dirk"],["dc.contributor.author","Post, Heiner"],["dc.contributor.author","Grossmann, Marius"],["dc.contributor.author","Doerge, Hilmar"],["dc.contributor.author","Gottlieb, Philip A."],["dc.contributor.author","Sachs, Frederick"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Schoendube, Friedrich Albert"],["dc.contributor.author","Pieske, Burkert M."],["dc.date.accessioned","2018-11-07T11:11:08Z"],["dc.date.available","2018-11-07T11:11:08Z"],["dc.date.issued","2008"],["dc.description.abstract","Aims Stretch is an important regulator of atrial function. The functional effects of stretch on human atrium, however, are poorly understood. Thus, we characterized the stretch-induced force response in human atrium and evaluated the underlying cellular mechanisms. Methods and results Isometric twitch force of human atrial trabeculae (n = 252) was recorded (37 C, 1 Hz stimulation) following stretch from 88 (L88) to 98% (L98) of optimal length. [Na(+)](i) and pH(i) were measured using SBFI and BCECF epifluorescence, respectively. Stretch induced a biphasic force increase: an immediate increase [first-phase, Frank-Starting mechanism (FSM)] to similar to 190% of force at L88 followed by an additional slower increase [5-10 min; stow force response (SFR)] to similar to 120% of the FSM. FSM and SFR were unaffected by gender, age, ejection fraction, and pre-medication with major cardiovascular drugs. There was a positive correlation between the amplitude of the FSM and the SFR. [Na(+)](i) rose by similar to 1 mmol/L and pH(i) remained unchanged during the SFR. Inhibition of Na(+)/H(+)-exchange (3 mu M HOE642), Na(+)/Ca(2+)-exchange (5 mu M KB-R7943), or stretch-activated channels (0.5 mu M, GsMtx-4 and 80 mu M streptomycin) did not reduce the SFR. Inhibition of angiotensin-II (AngII) receptors (5 mu M saralasin and 0.5 mu M PD123319) or pre-application of 0.5 mu M AngII, however, reduced the SFR by similar to 40-60%. Moreover, stretch increased phosphorylation of myosin tight chain 2 (MLC2a) and inhibition of MLC kinase (10 mu M ML-7 and 5 mu M wortmannin) decreased the SFR by similar to 40-85%. Conclusion Stretch elicits a SFR in human atrium. The atrial SFR is mediated by stretch-induced release and autocrine/paracrine actions of AngII and increased myofilament Ca(2+) responsiveness via phosphorylation of MLC2a by MLC kinase."],["dc.identifier.doi","10.1093/cvr/cvn126"],["dc.identifier.isi","000259301600014"],["dc.identifier.pmid","18503051"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6310"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53362"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0008-6363"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Angiotensin II and myosin light-chain phosphorylation contribute to the stretch-induced slow force response in human atrial myocardium"],["dc.type","journal_article"],["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"]]

[["dc.bibliographiccitation.artnumber","57"],["dc.bibliographiccitation.journal","Cardiovascular Diabetology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Fredersdorf, Sabine"],["dc.contributor.author","Thumann, Christian"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Vetter, Roland"],["dc.contributor.author","Graf, Tobias"],["dc.contributor.author","Luchner, Andreas"],["dc.contributor.author","Riegger, Guenter A. J."],["dc.contributor.author","Schunkert, Heribert"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Weil, Joachim"],["dc.date.accessioned","2017-09-07T11:48:52Z"],["dc.date.available","2017-09-07T11:48:52Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Calcium (Ca2+) handling proteins are known to play a pivotal role in the pathophysiology of cardiomyopathy. However little is known about early changes in the diabetic heart and the impact of insulin treatment (Ins). Methods: Zucker Diabetic Fatty rats treated with or without insulin (ZDF +/- Ins, n = 13) and lean littermates (controls, n = 7) were sacrificed at the age of 19 weeks. ZDF + Ins (n = 6) were treated with insulin for the last 6 weeks of life. Gene expression of Ca2+ ATPase in the cardiac sarcoplasmatic reticulum (SERCA2a, further abbreviated as SERCA) and phospholamban (PLB) were determined by northern blotting. Ca2+ transport of the sarcoplasmatic reticulum (SR) was assessed by oxalate-facilitated 45Ca-uptake in left ventricular homogenates. In addition, isolated neonatal cardiomyocytes were stimulated in cell culture with insulin, glucose or triiodthyronine (T3, positive control). mRNA expression of SERCA and PLB were measured by Taqman PCR. Furthermore, effects of insulin treatment on force of contraction and relaxation were evaluated by cardiomyocytes grown in a three-dimensional collagen matrix (engineered heart tissue, EHT) stimulated for 5 days by insulin. By western blot phosphorylations status of Akt was determed and the influence of wortmannin. Results: SERCA levels increased in both ZDF and ZDF + Ins compared to control (control 100 +/- 6.2 vs. ZDF 152 +/- 26.6 vs. ZDF + Ins 212 +/- 18.5 # % of control, p < 0.05 vs. control, #p < 0.05 vs. ZDF) whereas PLB was significantly decreased in ZDF and ZDF + Ins (control 100 +/- 2.8 vs. ZDF 76.3 +/- 13.5 vs. ZDF + Ins 79.4 +/- 12.9 % of control, p < 0.05 vs control). The increase in the SERCA/PLB ratio in ZDF and ZDF +/- Ins was accompanied by enhanced Ca2+ uptake to the SR (control 1.58 +/- 0.1 vs. ZDF 1.85 +/- 0.06 vs. ZDF + Ins 2.03 +/- 0.1 mu g/mg/min, p < 0.05 vs. control). Interestingly, there was a significant correlation between Ca2+ uptake and SERCA2a expression. As shown by in-vitro experiments, the effect of insulin on SERCA2a mRNA expression seemed to have a direct effect on cardiomyocytes. Furthermore, long-term treatment of engineered heart tissue with insulin increased the SERCA/PLB ratio and accelerated relaxation time. Akt was significantly phosphorylated by insulin. This effect could be abolished by wortmannin. Conclusion: The current data demonstrate that early type 2 diabetes is associated with an increase in the SERCA/PLB ratio and that insulin directly stimulates SERCA expression and relaxation velocity. These results underline the important role of insulin and calcium handling proteins in the cardiac adaptation process of type 2 diabetes mellitus contributing to cardiac remodeling and show the important role of PI3-kinase-Akt-SERCA2a signaling cascade."],["dc.identifier.doi","10.1186/1475-2840-11-57"],["dc.identifier.gro","3142533"],["dc.identifier.isi","000309125900001"],["dc.identifier.pmid","22621761"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7942"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8895"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: University of Regensburg"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1475-2840"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Increased myocardial SERCA expression in early type 2 diabetes mellitus is insulin dependent: In vivo and in vitro data"],["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","569"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.lastpage","571"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Wittkoepper, Katrin"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","El-Armouche, Ali"],["dc.date.accessioned","2018-11-07T08:39:30Z"],["dc.date.available","2018-11-07T08:39:30Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1007/s00395-010-0107-2"],["dc.identifier.isi","000280647500001"],["dc.identifier.pmid","20526608"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/4984"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19012"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","0300-8428"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Phosphatase-1-inhibitor-1: amplifier or attenuator of catecholaminergic stress?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1105"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","U46"],["dc.bibliographiccitation.volume","109"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Boy, Oliver"],["dc.contributor.author","Christalla, Peter"],["dc.contributor.author","Doeker, Stephan"],["dc.contributor.author","Naito, Hiroshi"],["dc.contributor.author","Karikkineth, Bijoy Chandapillai"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Grimm, Michael"],["dc.contributor.author","Nose, Monika"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Zieseniss, Anke"],["dc.contributor.author","Katschinski, Dörthe M."],["dc.contributor.author","Hamdani, Nazha"],["dc.contributor.author","Linke, Wolfgang A."],["dc.contributor.author","Yin, Xiaoke"],["dc.contributor.author","Mayr, Manuel"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2017-09-07T11:43:18Z"],["dc.date.available","2017-09-07T11:43:18Z"],["dc.date.issued","2011"],["dc.description.abstract","Rationale: Cardiac tissue engineering should provide \"realistic\" in vitro heart muscle models and surrogate tissue for myocardial repair. For either application, engineered myocardium should display features of native myocardium, including terminal differentiation, organotypic maturation, and hypertrophic growth. Objective: To test the hypothesis that 3D-engineered heart tissue (EHT) culture supports (1) terminal differentiation as well as (2) organotypic assembly and maturation of immature cardiomyocytes, and (3) constitutes a methodological platform to investigate mechanisms underlying hypertrophic growth. Methods and Results: We generated EHTs from neonatal rat cardiomyocytes and compared morphological and molecular properties of EHT and native myocardium from fetal, neonatal, and adult rats. We made the following key observations: cardiomyocytes in EHT (1) gained a high level of binucleation in the absence of notable cytokinesis, (2) regained a rod-shape and anisotropic sarcomere organization, (3) demonstrated a fetal-to-adult gene expression pattern, and (4) responded to distinct hypertrophic stimuli with concentric or eccentric hypertrophy and reexpression of fetal genes. The process of terminal differentiation and maturation (culture days 7-12) was preceded by a tissue consolidation phase (culture days 0-7) with substantial cardiomyocyte apoptosis and dynamic extracellular matrix restructuring. Conclusions: This study documents the propensity of immature cardiomyocytes to terminally differentiate and mature in EHT in a remarkably organotypic manner. It moreover provides the rationale for the utility of the EHT technology as a methodological bridge between 2D cell culture and animal models. (Circ Res. 2011;109:1105-1114.)"],["dc.identifier.doi","10.1161/CIRCRESAHA.111.251843"],["dc.identifier.gro","3142637"],["dc.identifier.isi","000296417200005"],["dc.identifier.pmid","21921264"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7826"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63"],["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.issn","0009-7330"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Terminal Differentiation, Advanced Organotypic Maturation, and Modeling of Hypertrophic Growth in Engineered Heart Tissue"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e14263"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Schwoerer, Alexander Peter"],["dc.contributor.author","Neuber, Christiane"],["dc.contributor.author","Emmons, Julius"],["dc.contributor.author","Biermann, Daniel"],["dc.contributor.author","Christalla, Thomas"],["dc.contributor.author","Grundhoff, Adam"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Ehmke, Heimo"],["dc.date.accessioned","2017-09-07T11:45:09Z"],["dc.date.available","2017-09-07T11:45:09Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Mechanical overload leads to cardiac hypertrophy and mechanical unloading to cardiac atrophy. Both conditions produce similar transcriptional changes including a re-expression of fetal genes, despite obvious differences in phenotype. MicroRNAs (miRNAs) are discussed as superordinate regulators of global gene networks acting mainly at the translational level. Here, we hypothesized that defined sets of miRNAs may determine the direction of cardiomyocyte plasticity responses. Methodology/Principal Findings: We employed ascending aortic stenosis (AS) and heterotopic heart transplantation (HTX) in syngenic Lewis rats to induce mechanical overloading and unloading, respectively. Heart weight was 26 +/- 3% higher in AS (n = 7) and 33 +/- 2% lower in HTX (n = 7) as compared to sham-operated (n = 6) and healthy controls (n = 7). Small RNAs were enriched from the left ventricles and subjected to quantitative stem-loop specific RT-PCR targeting a panel of 351 miRNAs. In total, 153 miRNAs could be unambiguously detected. Out of 72 miRNAs previously implicated in the cardiovascular system, 40 miRNAs were regulated in AS and/or HTX. Overall, HTX displayed a slightly broader activation pattern for moderately regulated miRNAs. Surprisingly, however, the regulation of individual miRNA expression was strikingly similar in direction and amplitude in AS and HTX with no miRNA being regulated in opposite direction. In contrast, fetal hearts from Lewis rats at embryonic day 18 exhibited an entirely different miRNA expression pattern. Conclusions: Taken together, our findings demonstrate that opposite changes in cardiac workload induce a common miRNA expression pattern which is markedly different from the fetal miRNA expression pattern. The direction of postnatal adaptive cardiac growth does, therefore, not appear to be determined at the level of single miRNAs or a specific set of miRNAs. Moreover, miRNAs themselves are not reprogrammed to a fetal program in response to changes in hemodynamic load."],["dc.identifier.doi","10.1371/journal.pone.0014263"],["dc.identifier.gro","3142819"],["dc.identifier.isi","000285135800004"],["dc.identifier.pmid","21151612"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6919"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/265"],["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","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Common MicroRNA Signatures in Cardiac Hypertrophic and Atrophic Remodeling Induced by Changes in Hemodynamic Load"],["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","470"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","474"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Rudolph, Volker"],["dc.contributor.author","Andrié, René P."],["dc.contributor.author","Rudolph, Tanja K."],["dc.contributor.author","Friedrichs, Kai"],["dc.contributor.author","Klinke, Anna"],["dc.contributor.author","Hirsch-Hoffmann, Birgit"],["dc.contributor.author","Schwoerer, Alexander P."],["dc.contributor.author","Lau, Denise"],["dc.contributor.author","Fu, XiaoMing"],["dc.contributor.author","Klingel, Karin"],["dc.contributor.author","Sydow, Karsten"],["dc.contributor.author","Didié, Michael"],["dc.contributor.author","Seniuk, Anika"],["dc.contributor.author","von Leitner, Eike-Christin"],["dc.contributor.author","Szoecs, Katalin"],["dc.contributor.author","Schrickel, Jan W."],["dc.contributor.author","Treede, Hendrik"],["dc.contributor.author","Wenzel, Ulrich"],["dc.contributor.author","Lewalter, Thorsten"],["dc.contributor.author","Nickenig, Georg"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Meinertz, Thomas"],["dc.contributor.author","Böger, Rainer H."],["dc.contributor.author","Reichenspurner, Hermann"],["dc.contributor.author","Freeman, Bruce A."],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Ehmke, Heimo"],["dc.contributor.author","Hazen, Stanley L."],["dc.contributor.author","Willems, Stephan"],["dc.contributor.author","Baldus, Stephan"],["dc.date.accessioned","2017-09-07T11:46:08Z"],["dc.date.available","2017-09-07T11:46:08Z"],["dc.date.issued","2010"],["dc.description.abstract","Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation(1). However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain elusive. Here we provide experimental and clinical evidence for the mechanistic involvement of myeloperoxidase (MPO), a heme enzyme abundantly expressed by neutrophils, in the pathophysiology of atrial fibrillation. MPO-deficient mice pretreated with angiotensin II (AngII) to provoke leukocyte activation showed lower atrial tissue abundance of the MPO product 3-chlorotyrosine, reduced activity of matrix metalloproteinases and blunted atrial fibrosis as compared to wild-type mice. Upon right atrial electrophysiological stimulation, MPO-deficient mice were protected from atrial fibrillation, which was reversed when MPO was restored. Humans with atrial fibrillation had higher plasma concentrations of MPO and a larger MPO burden in right atrial tissue as compared to individuals devoid of atrial fibrillation. In the atria, MPO colocalized with markedly increased formation of 3-chlorotyrosine. Our data demonstrate that MPO is a crucial prerequisite for structural remodeling of the myocardium, leading to an increased vulnerability to atrial fibrillation."],["dc.identifier.doi","10.1038/nm.2124"],["dc.identifier.gro","3142946"],["dc.identifier.isi","000276446800053"],["dc.identifier.pmid","20305660"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6269"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/406"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10. FU_Med"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1078-8956"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]