Maier, Lars Siegfried

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Stehle, Thea"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Knierim, Maria"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Holzamer, Andreas"],["dc.contributor.author","Hilker, Michael"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2020-12-10T14:10:25Z"],["dc.date.available","2020-12-10T14:10:25Z"],["dc.date.issued","2020"],["dc.description.abstract","Pharmacologic approaches for the treatment of atrial arrhythmias are limited due to side effects and low efficacy. Thus, the identification of new antiarrhythmic targets is of clinical interest. Recent genome studies suggested an involvement of SCN10A sodium channels (NaV1.8) in atrial electrophysiology. This study investigated the role and involvement of NaV1.8 (SCN10A) in arrhythmia generation in the human atria and in mice lacking NaV1.8. NaV1.8 mRNA and protein were detected in human atrial myocardium at a significant higher level compared to ventricular myocardium. Expression of NaV1.8 and NaV1.5 did not differ between myocardium from patients with atrial fibrillation and sinus rhythm. To determine the electrophysiological role of NaV1.8, we investigated isolated human atrial cardiomyocytes from patients with sinus rhythm stimulated with isoproterenol. Inhibition of NaV1.8 by A-803467 or PF-01247324 showed no effects on the human atrial action potential. However, we found that NaV1.8 significantly contributes to late Na+ current and consequently to an increased proarrhythmogenic diastolic sarcoplasmic reticulum Ca2+ leak in human atrial cardiomyocytes. Selective pharmacological inhibition of NaV1.8 potently reduced late Na+ current, proarrhythmic diastolic Ca2+ release, delayed afterdepolarizations as well as spontaneous action potentials. These findings could be confirmed in murine atrial cardiomyocytes from wild-type mice and also compared to SCN10A−/− mice (genetic ablation of NaV1.8). Pharmacological NaV1.8 inhibition showed no effects in SCN10A−/− mice. Importantly, in vivo experiments in SCN10A−/− mice showed that genetic ablation of NaV1.8 protects against atrial fibrillation induction. This study demonstrates that NaV1.8 is expressed in the murine and human atria and contributes to late Na+ current generation and cellular arrhythmogenesis. Blocking NaV1.8 selectively counteracts this pathomechanism and protects against atrial arrhythmias. Thus, our translational study reveals a new selective therapeutic target for treating atrial arrhythmias."],["dc.identifier.doi","10.1007/s00395-020-0780-8"],["dc.identifier.pmid","32078054"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70756"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/349"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.rights","CC BY 4.0"],["dc.title","Inhibition of NaV1.8 prevents atrial arrhythmogenesis in human and mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","673"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","680"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Schillinger, Wolfgang"],["dc.contributor.author","Teucher, Nils"],["dc.contributor.author","Christians, Claus"],["dc.contributor.author","Kohlhaas, Michael"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Van Nguyen, Phuc"],["dc.contributor.author","Schmidt, Albrecht G."],["dc.contributor.author","Schunck, Ortwin"],["dc.contributor.author","Nebendahl, Klaus"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Zeitz, Oliver"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.date.accessioned","2017-09-07T11:52:27Z"],["dc.date.available","2017-09-07T11:52:27Z"],["dc.date.issued","2006"],["dc.description.abstract","We investigated the hypothesis that increased intracellular [Na+](i) in heart failure contributes to preservation of SR Ca2+ load which may become particularly evident at slow heart rates. [Na+]i in SBFI-loaded myocytes from rabbits with pacing-induced heart failure (PHF) was significantly higher at each frequency as compared to Sham-operated animals. Furthermore, PHF rabbits demonstrated reduced SR Ca2+-ATPase protein levels (-37%, p < 0.04) but unchanged Na+/Ca2+ exchanger protein levels. At 0.25 Hz, isometric force was similar in cardiac trabeculae from PHF rabbits as compared to control (PHF, 3.6 +/- 1.3; Sham, 4.4 +/- 0.6 mN/mm(2)). Rapid cooling contractures (RCCs) were unchanged indicating preserved SR Ca2+ load at this frequency. In Sham, isometric twitch force increased with rising frequencies to 29.0 +/- 2.8 mN/mm(2) at 3.0 Hz (p < 0.05) as compared to 0.25 Hz. RCCs showed a parallel increase by 186 +/- 47% (p < 0.01). In PHF, frequency-dependent increase in force (15.8 +/- 4.7 mN/mm(2) at 3.0 Hz) and RCCs (increase by 70 +/- 40%) were significantly blunted. Thus, in PHF in rabbits SR Ca2+ load is preserved at low frequencies despite decreased SR Ca2+-ATPase expression. This may result from [Na+](i)-dependent changes in Na+/Ca2+ exchanger activity. (c) 2006 European Society of Cardiology. Published by Elsevier B.V All rights reserved."],["dc.identifier.doi","10.1016/j.ejheart.2006.01.013"],["dc.identifier.gro","3143598"],["dc.identifier.isi","000242383300002"],["dc.identifier.pmid","16540370"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1130"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1388-9842"],["dc.title","High intracellular Na+ preserves myocardial function at low heart rates in isolated myocardium from failing hearts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","267"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Clinical Research in Cardiology"],["dc.bibliographiccitation.lastpage","276"],["dc.bibliographiccitation.volume","99"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Pelster, Theresa"],["dc.contributor.author","Pax, Anja"],["dc.contributor.author","Horn, Wiebke"],["dc.contributor.author","Schmidt-Schweda, Stephan"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Seidler, Tim"],["dc.contributor.author","Wagner, Stephan"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:46:04Z"],["dc.date.available","2017-09-07T11:46:04Z"],["dc.date.issued","2010"],["dc.description.abstract","Post-cardiac arrest myocardial dysfunction is a common phenomenon after return of spontaneous circulation (ROSC) and contributes to hemodynamic instability and low survival rates after cardiac arrest. Mild hypothermia for 24 h after ROSC has been shown to significantly improve neurologic recovery and survival rates. In the present study we investigate the influence of therapeutic hypothermia on hemodynamic parameters in resuscitated patients and on contractility in failing human myocardium. We analyzed hemodynamic data from 200 cardiac arrest survivors during the hypothermia period. The initial LVEF was 32.6 +/- A 1.2% indicating a significantly impaired LV function. During hypothermia induction, the infusion rate of epinephrine could be significantly reduced from 9.1 +/- A 1.3 mu g/min [arrival intensive care unit (ICU) 35.4A degrees C] to 4.6 +/- A 1.0 mu g/min (34A degrees C) and 2.8 +/- A 0.5 mu g/min (33A degrees C). The dobutamine and norepinephrine application rates were not changed significantly. The mean arterial blood pressure remained stable. The mean heart rate significantly decreased from 91.8 +/- A 1.7 bpm (arrival ICU) to 77.3 +/- A 1.5 bpm (34A degrees C) and 70.3 +/- A 1.4 bpm (33A degrees C). In vitro we investigated the effect of hypothermia on isolated ventricular muscle strips from explanted failing human hearts. With decreasing temperature, the contractility increased to a maximum of 168 +/- A 23% at 27A degrees C (n = 16, P < 0.05). Positive inotropic response to hypothermia was accompanied by moderately increased rapid cooling contractures as a measure of sarcoplasmic reticulum (SR) Ca(2+) content, but can be elicited even when the SR Ca(2+) release is blocked in the presence of ryanodine. Contraction and relaxation kinetics are prolonged with hypothermia, indicating increased Ca(2+) sensitivity as the main mechanism responsible for inotropy. In conclusion, mild hypothermia stabilizes hemodynamics in cardiac arrest survivors which might contribute to improved survival rates in these patients. Mechanistically, we demonstrate that hypothermia improves contractility in failing human myocardium most likely by increasing Ca(2+)-sensitivity."],["dc.identifier.doi","10.1007/s00392-010-0113-2"],["dc.identifier.gro","3142931"],["dc.identifier.isi","000277014600001"],["dc.identifier.pmid","20130890"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/4240"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/389"],["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","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","1861-0684"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","32"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","43"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Rasenack, Eva C. L."],["dc.contributor.author","Ruff, Hanna"],["dc.contributor.author","Weber, Sarah L."],["dc.contributor.author","Schoendube, Friedrich A."],["dc.contributor.author","Tirilomis, Theodor"],["dc.contributor.author","Tenderich, Gero"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:48:16Z"],["dc.date.available","2017-09-07T11:48:16Z"],["dc.date.issued","2008"],["dc.description.abstract","The goal of this study was to test the hypothesis that the novel anti-ischemic drug ratiolazine, which is known to inhibit late I-Na, could reduce intracellular [Na+](i) and diastolic [Ca2+](i) overload and improve diastolic function. Contractile dysfunction in human heart failure (HF) is associated with increased [Na+](i) and elevated diastolic [Ca2+](i). Increased Na influx through voltage-gated Na+ channels (late I-Na) has been suggested to contribute to elevated [Na+](i) in HF. In isometrically contracting ventricular muscle strips from end-stage failing human hearts, ranolazine (10 mu mol/L) did not exert negative inotropic effects on twitch force amplitude. However, ranolazine significantly reduced frequency-dependent increase in diastolic tension (i.e., diastolic dysfunction) by similar to 30% without significantly affecting sarcoplasmic reticulum (SR) Ca2+ loading. To investigate the mechanism of action of this beneficial effect of ranolazine on diastolic tension, Anemonia sulcata toxin II (ATX-II, 40 nmol/L) was used to increase intracellular Na+ loading in ventricular rabbit myocytes. ATX-II caused a significant rise in [Na+](i) typically seen in heart failure via increased late I-Na. In parallel, ATX-II significantly increased diastolic [Ca2+](i). In the presence of ranolazine the increases in late I-Na, as well as [Na+](i) and diastolic [Ca2+](i) were significantly blunted at all stimulation rates without significantly decreasing Ca2+ transient amplitudes or SR Ca2+ content. In summary, ranolazine reduced the frequency dependent increase in diastolic tension without having negative inotropic effects on contractility of muscles from end-stage failing human hearts. Moreover, in rabbit myocytes the increases in late I-Na, [Na+](i) and [Ca2+](i) caused by ATX-II, were significantly blunted by ranolazine. These results suggest that ratiolazine may be of therapeutic benefit in conditions of diastolic dysfunction due to elevated [Na+](i) and diastolic [Ca2+](i). (C) 2008 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2008.03.006"],["dc.identifier.gro","3143272"],["dc.identifier.isi","000257543800004"],["dc.identifier.pmid","18439620"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/767"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Ltd- Elsevier Science Ltd"],["dc.relation.eissn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.title","Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts - Role of late sodium current and intracellular ion accumulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","6965"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Sprenger, Julia U."],["dc.contributor.author","Perera, Ruwan K."],["dc.contributor.author","Steinbrecher, Julia H."],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.date.accessioned","2017-09-07T11:44:27Z"],["dc.date.available","2017-09-07T11:44:27Z"],["dc.date.issued","2015"],["dc.description.abstract","3',5'-cyclic adenosine monophosphate (cAMP) is an ubiquitous second messenger that regulates physiological functions by acting in distinct subcellular microdomains. Although several targeted cAMP biosensors are developed and used in single cells, it is unclear whether such biosensors can be successfully applied in vivo, especially in the context of disease. Here, we describe a transgenic mouse model expressing a targeted cAMP sensor and analyse microdomain-specific second messenger dynamics in the vicinity of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). We demonstrate the bio-compatibility of this targeted sensor and its potential for real-time monitoring of compartmentalized cAMP signalling in adult cardiomyocytes isolated from a healthy mouse heart and from an in vivo cardiac disease model. In particular, we uncover the existence of a phos-phodiesterase-dependent receptor-microdomain communication, which is affected in hypertrophy, resulting in reduced beta-adrenergic receptor-cAMP signalling to SERCA."],["dc.identifier.doi","10.1038/ncomms7965"],["dc.identifier.gro","3141928"],["dc.identifier.isi","000353704700017"],["dc.identifier.pmid","25917898"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2634"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/103"],["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 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.title","In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.volume","87"],["dc.contributor.author","Fluschnik, Nina"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Ort, Katharina R."],["dc.contributor.author","Neef, S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars. S."],["dc.date.accessioned","2018-11-07T08:41:33Z"],["dc.date.available","2018-11-07T08:41:33Z"],["dc.date.issued","2010"],["dc.format.extent","S93"],["dc.identifier.isi","000282114100226"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19494"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","0008-6363"],["dc.title","Beneficial effects of CaMKII inhibition in the human failing heart"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.volume","59"],["dc.contributor.author","Maier, Lars"],["dc.contributor.author","Wachter, R. Rolf"],["dc.contributor.author","Edelmann, Frank T."],["dc.contributor.author","Layug, Beth"],["dc.contributor.author","Karwatowska-Prokopczuk, Ewa"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.date.accessioned","2018-11-07T09:12:09Z"],["dc.date.available","2018-11-07T09:12:09Z"],["dc.date.issued","2012"],["dc.format.extent","E865"],["dc.identifier.isi","000302326700868"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26885"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.publisher.place","New york"],["dc.relation.eventlocation","Chicago, IL"],["dc.relation.issn","0735-1097"],["dc.title","RANOLAZINE FOR THE TREATMENT OF DIASTOLIC HEART FAILURE IN PATIENTS WITH PRESERVED EJECTION FRACTION: RESULTS FROM THE RALI-DHF STUDY"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","194"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.lastpage","199"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hermann, Hans-Peter"],["dc.contributor.author","Luers, C."],["dc.contributor.author","Hünlich, Mark"],["dc.contributor.author","Zeitz, Oliver"],["dc.contributor.author","Janssen, P. M. L."],["dc.contributor.author","Pieske, Burkert"],["dc.date.accessioned","2017-09-07T11:45:57Z"],["dc.date.available","2017-09-07T11:45:57Z"],["dc.date.issued","2002"],["dc.description.abstract","Background-Application of pyruvate was shown to improve contractile function in isolated animal myocardium and hemodynamics in patients with congestive heart failure. We assessed the influence of pyruvate on systolic and diastolic myocardial function and its subcellular mode of action in isolated myocardium. from end-stage failing human hearts. Methods and Results-In muscle strip preparations, concentration-dependent effects of pyruvate on developed and diastolic force (n=6), aequorin light emission reflecting intracellular Ca2+ transients (n=6), and rapid cooling contractures reflecting sarcoplasmic reticulum (SR) Ca2+ content (n=11) were measured. Pyruvate resulted in a concentration-dependent increase in developed force and a decrease in diastolic force, with a maximum effect of 155% and 21%, respectively, at 20 mmol/L pyruvate (P<0.05). This was associated with a dose-dependent prolongation of time to peak tension and relaxation time. Pyruvate increased rapid cooling contractures by 51% and aequorin light signals by 85% (at 15 and 20 mmol/L; P<0.05). This indicates increased SR Ca2+ content and increased intracellular Ca2+ transients. The inotropic effect of pyruvate was still present after elimination of SR Ca2+ storage function with 10 mumol/L cyclopiazonic acid and I mumol/L ryanodine (n=8). Pyruvate significantly increased intracellular pH from 7.31+/-0.03 to 7.40+/-0.04 by BCECF fluorescence (n=6). Conclusions-The present findings indicate that pyruvate improves contractile performance of failing human myocardium by increasing a intracellular Ca2+ transients as well as myofilament Ca2+ sensitivity. The former seem to result from increased SR Ca2+ accumulation and release, the latter from increased intracellular pH."],["dc.identifier.doi","10.1161/hc0202.102238"],["dc.identifier.gro","3144225"],["dc.identifier.isi","000173330900027"],["dc.identifier.pmid","11790700"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1826"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0009-7322"],["dc.title","Influence of pyruvate on contractile performance and Ca2+ cycling in isolated failing human myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","507"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.lastpage","517"],["dc.bibliographiccitation.volume","118"],["dc.contributor.author","Mauritz, Christina"],["dc.contributor.author","Schwanke, Kristin"],["dc.contributor.author","Reppel, Michael"],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Katsirntaki, Katherina"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Nguemo, Filomain"],["dc.contributor.author","Menke, Sandra"],["dc.contributor.author","Haustein, Moritz"],["dc.contributor.author","Hescheler, Juergen"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Martin, Ulrich"],["dc.date.accessioned","2017-09-07T11:48:16Z"],["dc.date.available","2017-09-07T11:48:16Z"],["dc.date.issued","2008"],["dc.description.abstract","Background - The recent breakthrough in the generation of induced pluripotent stem ( iPS) cells, which are almost indistinguishable from embryonic stem ( ES) cells, facilitates the generation of murine disease - and human patient specific stem cell lines. The aim of this study was to characterize the cardiac differentiation potential of a murine iPS cell clone in comparison to a well- established murine ES cell line. Methods and Results - With the use of a standard embryoid body - based differentiation protocol for ES cells, iPS cells as well as ES cells were differentiated for 24 days. Although the analyzed iPS cell clone showed a delayed and less efficient formation of beating embryoid bodies compared with the ES cell line, the differentiation resulted in an average of 55% of spontaneously contracting iPS cell embryoid bodies. Analyses on molecular, structural, and functional levels demonstrated that iPS cell - derived cardiomyocytes show typical features of ES cell - derived cardiomyocytes. Reverse transcription polymerase chain reaction analyses demonstrated expression of marker genes typical for mesoderm, cardiac mesoderm, and cardiomyocytes including Brachyury, mesoderm posterior factor 1 ( Mesp1), friend of GATA2 ( FOG- 2), GATA-binding protein 4 ( GATA4), NK2 transcription factor related, locus 5 ( Nkx2.5), T-box 5 (Tbx5), T- box 20 ( Tbx20), atrial natriuretic factor ( ANF), myosin light chain 2 atrial transcripts ( MLC2a), myosin light chain 2 ventricular transcripts (MLC2v), alpha-myosin heavy chain (alpha-MHC), and cardiac troponin T in differentiation cultures of iPS cells. Immunocytology confirmed expression of cardiomyocyte-typical proteins including sarcomeric alpha-actinin, titin, cardiac troponin T, MLC2v, and connexin 43. iPS cell cardiomyocytes displayed spontaneous rhythmic intracellular Ca2+ fluctuations with amplitudes of Ca2+ transients comparable to ES cell cardiomyocytes. Simultaneous Ca2+ release within clusters of iPS cell - derived cardiomyocytes indicated functional coupling of the cells. Electrophysiological studies with multielectrode arrays demonstrated functionality and presence of the beta- adrenergic and muscarinic signaling cascade in these cells. Conclusions - iPS cells differentiate into functional cardiomyocytes. In contrast to ES cells, iPS cells allow derivation of autologous functional cardiomyocytes for cellular cardiomyoplasty and myocardial tissue engineering."],["dc.identifier.doi","10.1161/CIRCULATIONAHA.108.778795"],["dc.identifier.gro","3143267"],["dc.identifier.isi","000257994500008"],["dc.identifier.pmid","18625890"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/762"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0009-7322"],["dc.title","Generation of functional murine cardiac myocytes from induced pluripotent stem cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Streckfuss-Boemeke, Katrin"],["dc.contributor.author","Fischer, C."],["dc.contributor.author","Stauske, Michael"],["dc.contributor.author","Perret, A."],["dc.contributor.author","Oezcelic, C."],["dc.contributor.author","Wagner, S."],["dc.contributor.author","Maier, Lars. S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Guan, Kaomei"],["dc.date.accessioned","2018-11-07T09:37:39Z"],["dc.date.available","2018-11-07T09:37:39Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1093/cvr/cvu083.2"],["dc.identifier.isi","000343730100211"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32886"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","Barcelona, SPAIN"],["dc.relation.issn","1755-3245"],["dc.relation.issn","0008-6363"],["dc.title","RBM20-dependent regulation of organized myofilament structure and titin splicing in induced pluripotent stem cell-derived cardiomyocytes from patients with dilative cardiomyopathy"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]