Grimm, Michael

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

[["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.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.firstpage","250"],["dc.bibliographiccitation.issue","2-3"],["dc.bibliographiccitation.journal","Progress in Biophysics and Molecular Biology"],["dc.bibliographiccitation.lastpage","267"],["dc.bibliographiccitation.volume","97"],["dc.contributor.author","Kockskaemper, Jens"],["dc.contributor.author","von Lewinski, Dirk"],["dc.contributor.author","Khafaga, Mounir"],["dc.contributor.author","Eigner, Andreas"],["dc.contributor.author","Grimm, Michael"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Gottlieb, Philip A."],["dc.contributor.author","Sachs, Frederick"],["dc.contributor.author","Pieske, Burkert M."],["dc.date.accessioned","2018-11-07T11:14:55Z"],["dc.date.available","2018-11-07T11:14:55Z"],["dc.date.issued","2008"],["dc.description.abstract","Mechanical load is an important regulator of cardiac force. Stretching human atrial and ventricular trabeculae elicited a biphasic force increase: an immediate increase (Frank-Starling mechanism) followed by a further slow increase (slow force response, SFR). In ventricle, the SFR was unaffected by AT- and ET-receptor antagonism, by inhibition of protein-kinase-C, PI-3-kinase, and NO-synthase, but attenuated by inhibition of Na+/H+- (NHE) and Na+/Ca2+-exchange (NCX). In atrium, however, neither NHE- nor NCX-inhibition affected the SFR. Stretch elicited a large NHE-dependent [Na+](i) increase in ventricle but only a small, NHE-independent [Na+]i increase in atrium. Stretch-activated non-selective cation channels contributed to basal force development in atrium but not ventricle and were not involved in the SFR in either tissue. Interestingly, inhibition of AT receptors or pre-application of angiotensin II or endothelin-1 reduced the atrial SFR. Furthermore, stretch increased phosphorylation of atrial myosin light chain 2 (MLC2) and inhibition of myosin light chain kinase (MLCK) attenuated the SFR in atrium and ventricle. Thus, in human heart both atrial and ventricular myocardium exhibit a stretch-dependent SFR that might serve to adjust cardiac output to increased workload. In ventricle, there is a robust NHE-dependent (but angiotensin II- and endothelin-1-independent) [Na+](i) increase that is translated into a [Ca2+](i) and force increase via NCX. In atrium, on the other hand, there is an angiotensin II- and endothelin-dependent (but NHE- and NCX-independent) force increase. Increased myofilament Ca2+ sensitivity through MLCK-induced phosphorylation of MLC2 is a novel mechanism contributing to the SFR in both atrium and ventricle. (c) 2008 Elsevier Ltd. All rights reserved."],["dc.description.sponsorship","NHLBI NIH HHS [R01 HL054887, R01 HL054887-13S1]"],["dc.identifier.doi","10.1016/j.pbiomolbio.2008.02.026"],["dc.identifier.isi","000257918100007"],["dc.identifier.pmid","18466959"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54253"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0079-6107"],["dc.title","The slow force response to stretch in atrial and ventricular myocardium from human heart: Functional relevance and subcellular mechanisms"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","396"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","406"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Wittkoepper, Katrin"],["dc.contributor.author","Degenhardt, Franziska"],["dc.contributor.author","Weinberger, Florian"],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Melnychenko, Ivan"],["dc.contributor.author","Grimm, Michael"],["dc.contributor.author","Peeck, Micha"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Dobrev, Dobromir"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.date.accessioned","2017-09-07T11:48:07Z"],["dc.date.available","2017-09-07T11:48:07Z"],["dc.date.issued","2008"],["dc.description.abstract","Phosphatase inhibitor-1 (I-1) is a conditional amplifier of beta-adrenergic signalling downstream of protein kinase A by inhibiting type-1 phosphatases only in its PKA-phosphorylated form. I-1 is downregulated in failing hearts and thus contributes to beta-adrenergic desensitization. It is unclear whether this should be viewed as a predominantly adverse or protective response. We generated transgenic mice with cardiac-specific I-1 overexpression (I-1-TG) and evaluated cardiac function and responses to catecholamines in mice with targeted disruption of the I-1 gene (I-1-KO). Both groups were compared with their wild-type (WT) littermates. I-1-TG developed cardiac hypertrophy and mild dysfunction which was accompanied by a substantial compensatory increase in PP1 abundance and activity, confounding cause-effect relationships. I-1-KO had normal heart structure with mildly reduced sensitivity, but unchanged maximal contractile responses to beta-adrenergic stimulation, both in vitro and in vivo. Notably, I-1-KO were partially protected from lethal catecholamine-induced arrhythmias and from hypertrophy and dilation induced by a 7 day infusion with the beta-adrenergic agonist isoprenaline. Moreover, I-1-KO exhibited a partially preserved acute beta-adrenergic response after chronic isoprenaline, which was completely absent in similarly treated WT. At the molecular level, I-1-KO showed lower steady-state phosphorylation of the cardiac ryanodine receptor/Ca(2+) release channel and the sarcoplasmic reticulum (SR) Ca(2+)-ATPase-regulating protein phospholamban. These alterations may lower the propensity for diastolic Ca(2+) release and Ca(2+) uptake and thus stabilize the SR and account for the protection. Taken together, loss of I-1 attenuates detrimental effects of catecholamines on the heart, suggesting I-1 downregulation in heart failure as a beneficial desensitization mechanism and I-1 inhibition as a potential novel strategy for heart failure treatment."],["dc.identifier.doi","10.1093/cvr/cvn208"],["dc.identifier.gro","3143199"],["dc.identifier.isi","000260973500012"],["dc.identifier.pmid","18689792"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/687"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0008-6363"],["dc.title","Phosphatase inhibitor-1-deficient mice are protected from catecholamine-induced arrhythmias and myocardial hypertrophy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]