Prestle, Jürgen

[["dc.bibliographiccitation.firstpage","486"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","494"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Baudet, S."],["dc.contributor.author","Weisser, J"],["dc.contributor.author","Janssen, A. P."],["dc.contributor.author","Beulich, K ."],["dc.contributor.author","Bieligk, U."],["dc.contributor.author","Pieske, Burkert"],["dc.contributor.author","Noireaud, J"],["dc.contributor.author","Janssen, P. M. L."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Prestle, J."],["dc.date.accessioned","2017-09-07T11:46:07Z"],["dc.date.available","2017-09-07T11:46:07Z"],["dc.date.issued","2001"],["dc.description.abstract","Objective: Protein kinase C (PKC) is thought to be involved in the regulation of the mammalian cardiac excitation-contraction coupling process by vasoactive peptides Like endothelin-1 (ET-1). However, the demonstration of a causal link between activation of specific PKC isoforms and the increase in contractility mediated by ET-1 is still inferential. Methods: By means of adenovirus-mediated gene transfer, we specifically overexpressed PKC epsilon in cultured adult rabbit Ventricular myocytes (Ad-PKC epsilon). Myocyte shortening and [Ca2+](i) transients under basal and ET-1-stimulated conditions were measured in Ad-PKC epsilon and Ad-LacZ control transfected cells. Results: Infection with Ad-PKC epsilon resulted in a strong, virus dose-dependent increase in PKC epsilon protein Levels, whereas protein expression of other PKC isoforms remained unchanged. Using a multiplicity of infection of 100 plaque-forming units/myocyte, basal and cofactor-dependent PKC epsilon kinase activity was increased 28- and 90-fold, respectively, when compared to control. Myocyte basal fractional shortening and [Ca2+](i), transient amplitude were both increased by 21% (P<0.05 each) in Ad-PKC transfected myocytes when compared to Ad-LacZ transfected control myocytes. The positive Inotropic effect of ET-1 in control myocytes was markedly blunted in PKC epsilon -overexpressing myocytes. Conclusion: Specific overexpression of PKC epsilon in rabbit ventricular myocytes increases basal myocyte contractility and [Ca2+](i) transients, and modifies their responsiveness to ET-1. (C) 2001 Elsevier Science B.V. AII rights reserved."],["dc.identifier.doi","10.1016/S0008-6363(01)00225-5"],["dc.identifier.gro","3144281"],["dc.identifier.isi","000168918600010"],["dc.identifier.pmid","11376624"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1887"],["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","0008-6363"],["dc.title","Increased basal contractility of cardiomyocytes overexpressing protein kinase C epsilon and blunted positive inotropic response to endothelin-1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","H349"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","American Journal of Physiology - Heart and Circulatory Physiology"],["dc.bibliographiccitation.lastpage","H356"],["dc.bibliographiccitation.volume","282"],["dc.contributor.author","Janssen, P. M. L."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Zeitz, Oliver"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.contributor.author","Prestle, J."],["dc.contributor.author","Darmer, D."],["dc.contributor.author","Holtz, J."],["dc.contributor.author","Schumann, H."],["dc.date.accessioned","2017-09-07T11:52:36Z"],["dc.date.available","2017-09-07T11:52:36Z"],["dc.date.issued","2002"],["dc.description.abstract","Increased mechanical load has been proposed as an inductor of apoptosis, but it is unknown whether this can occur in the range of pre- and afterloads that prevail in the beating heart. We investigated apoptosis in cultured rabbit multicellular myocardial preparations over several days. Muscles contracted in absence of pre- and afterload (unloaded isotonic), in absence of preload but in presence of afterload (unloaded isometric), or in presence of both (loaded isometric). After up to 48 h of continuous contractions, apoptosis was assessed by TdT-mediated nick-end labeling (TUNEL) assay and DNA ladder analysis. In muscles that contracted loaded isometric, apoptosis was detected after 6–24 h. After 48 h, apoptosis was most prominent in this group, reflected by a high level of DNA ladder intensity (DLI; 27.8 ± 11.5), whereas Bcl-xL (on RNA level) was significantly downregulated, and Fas remained unchanged. In unloaded isometric preparations, apoptosis was significantly less (6.9 ± 5.9 DLI) and very similar to those contracting unloaded isotonic (6.1 ± 5.1 DLI). We conclude that load-dependent apoptosis can occur at sarcomere lengths achievable in vivo and may mainly result from increased preload."],["dc.identifier.doi","10.1152/ajpheart.00024.2001"],["dc.identifier.gro","3144976"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2661"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","zu prüfen"],["dc.relation.issn","0363-6135"],["dc.title","Load-dependent induction of apoptosis in multicellular myocardial preparations"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","PII S0008-6363(02)00406-6"],["dc.bibliographiccitation.firstpage","300"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","308"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Janssen, P. M. L."],["dc.contributor.author","Schillinger, Wolfgang"],["dc.contributor.author","Donahue, J. K."],["dc.contributor.author","Zeitz, Oliver"],["dc.contributor.author","Embry, S. L."],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Weil, Joachim"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Prestle, J."],["dc.date.accessioned","2017-09-07T11:45:18Z"],["dc.date.available","2017-09-07T11:45:18Z"],["dc.date.issued","2002"],["dc.description.abstract","Objective: Increased levels of inhibitory G proteins have been observed in heart failure, but their physiological relevance in mediating the reduced P-adrenergic response is largely unknown. Methods: To evaluate the functional consequences of Gait overexpression, we studied myocardial contraction in intact isometric contracting cardiac rabbit trabeculae and isolated myocytes after adenovirus-mediated gene transfer of Galpha(i2). Results: Neither Galpha(i2) nor lacZ (control) overexpression altered baseline contractile force. After 72 h of continuous contractions, developed force (F-dev) increased after addition of 1 muM isoproterenol by 28.5 +/- 9.7 mN/mm(2) in the control group, which was unchanged from the initial response at t=0 h (23.7 +/- 3.8 mN/mm(2)). In sharp contrast, in preparations transfected with AdGalpha(i2), the response to isoproterenol was significantly attenuated (5.9 +/- 2.0 vs. 27.6 +/- 4.2 mN/mm(2), t=72 vs. 0 h, respectively, P<0.01). In a primary culture of transfected isolated myocytes from a nearly identical baseline, isoproterenol increased cell shortening by 3.1 +/- 0.6% in the lacZ transfected myocytes, but only by 1.3 +/- 0.5% in Galpha(i2) transfected myocytes (1=72 h, P<0.01). In Galpha(i2) transfected myocytes, pertussis toxin restored beta-adrenergic responsiveness, indicating specificity of attenuation by the transgene. Conclusions: Overexpression of Galpha(i2) attenuates the positive inotropic effects of beta-adrenergic stimulation in myocardium. In addition, the method we developed allows investigation of a causal link between altered protein expression and subsequent alterations in contractile function in a physiological relevant in vitro manner. (C) 2002 Elsevier Science B.V. All rights reserved."],["dc.identifier.doi","10.1016/S0008-6363(02)00406-6"],["dc.identifier.gro","3144181"],["dc.identifier.isi","000177355500014"],["dc.identifier.pmid","12123769"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1776"],["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","0008-6363"],["dc.title","Intracellular beta-blockade: overexpression of G alpha(i2) depresses the beta-adrenergic response in intact myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1419"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","1427"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Janssen, P. M. L."],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Prestle, J."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.date.accessioned","2017-09-07T11:47:28Z"],["dc.date.available","2017-09-07T11:47:28Z"],["dc.date.issued","1999"],["dc.description.abstract","Functional studies of different human cell types have been successfully conducted under in vitro conditions. Despite many efforts, it has not been possible to develop a human myocardial preparation in which contractile function can be studied over several days. We hypothesize that by mimicking the in vivo situation in an in vitro environment we can preserve viability and function of human myocardial preparations over several days. From explanted hearts of patients undergoing cardiac transplantation, multicellular preparations were dissected and mounted in a sterile muscle chamber, Muscles were stimulated at 0.5 or 1 Hz at 1.75 mmol/l Ca2+, a pH of 7.4 and at 37 degrees C, and kept contracting isometrically for 2-6 days. This study shows for the first time that contractile function of human myocardial tissue can be preserved over several days; active force development had not significantly changed after 48 h (10.6 +/- 1.2 at t = 0 v 11.4 +/- 2.8 mN/mm(2) at t = 48, n = 10), nor had diastolic force (1.0 +/- 0.1 v 0.9 +/- 0,1 mN/mm(2)), After at least 48 h, the contractile response to stimulation with I mu mol/l isoproterenol was clearly present: developed force increased to 631 +/- 146% of control values, while half-relaxation time declined to 57 +/- 6% (n = 7). In addition. both pharmacological responses and regulatory physiological behavior, such as post-rest potentiation and force-frequency relationships, are preserved. This technique allows the study of the regulation of contractile function of human myocardium in vitro and may be used to link changes in protein expression to consequent changes in myocardial contraction. (C) 1999 Academic Press."],["dc.identifier.doi","10.1006/jmcc.1999.0978"],["dc.identifier.gro","3144452"],["dc.identifier.isi","000081725400003"],["dc.identifier.pmid","10423340"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2077"],["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","Preservation of contractile characteristics of human myocardium in multi-day cell culture"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","H986"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","American Journal of Physiology-Heart and Circulatory Physiology"],["dc.bibliographiccitation.lastpage","H991"],["dc.bibliographiccitation.volume","279"],["dc.contributor.author","Lehnart, S. E."],["dc.contributor.author","Janssen, P. M. L."],["dc.contributor.author","Franz, W. M."],["dc.contributor.author","Donahue, J. K."],["dc.contributor.author","Lawrence, J. H."],["dc.contributor.author","Marbán, E."],["dc.contributor.author","Prestle, J."],["dc.contributor.author","Hasenfuß, G."],["dc.date.accessioned","2021-06-01T10:47:42Z"],["dc.date.available","2021-06-01T10:47:42Z"],["dc.date.issued","2000"],["dc.description.abstract","Adenoviral gene transfer to the heart represents a promising model for structure-function analyses. Rabbit hearts were subjected to an ex vivo perfusion protocol that achieves gene transfer in >90% of cardiac myocytes. Contractile function of isolated myocardial preparations of these hearts was then observed for 2 days in a recently developed trabecula culture system. In sham-infected hearts, the initial developed force (F init ) (15.6 ± 3.7 mN/mm 2 ; n = 12) did not change significantly after 48 h (17.0 ± 1.9 mN/mm 2 ; P = 0.46). In adenovirus-infected preparations, F init (14.3 ± 1.8 mN/mm 2 ; n = 21) did not significantly differ from the control ( P = 0.75) and was unchanged after 48 h (15.3 ± 2.5 mN/mm 2 ; P= 0.93). After 2 days of continuous contractions, we observed homogenous and high-level expression of the reporter genes LacZ coding for β-galactosidase and Luc coding for firefly luciferase. Luciferase activity increased more than 2,500-fold from background levels of 8.7 × 10 3 ± 5.0 × 10 3 relative light units (RLU)/mg protein (from hearts transfected with promotorless adenovirus with luciferase transgene construct AdNULLLuc, n = 5) to 23.4 × 10 6 ± 11.1 × 10 6 RLU/mg protein (from hearts tranfected with adenovirus with Rous sarcoma virus promotor and luciferase transgene construct AdRSVLuc, n = 5) in infected myocardial preparations ( P < 0.005). Our results demonstrate a new ex vivo approach to achieve homogenous and high-level expression of recombinant adenoviral genes in contracting myocardium without adverse functional effects."],["dc.identifier.doi","10.1152/ajpheart.2000.279.3.H986"],["dc.identifier.gro","3144358"],["dc.identifier.isi","000089379400015"],["dc.identifier.pmid","10993759"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85690"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","American Physiological Society"],["dc.relation.eissn","1522-1539"],["dc.relation.issn","0363-6135"],["dc.title","Preservation of myocardial function after adenoviral gene transfer in isolated myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","H1481"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","American Journal of Physiology-Heart and Circulatory Physiology"],["dc.bibliographiccitation.lastpage","H1488"],["dc.bibliographiccitation.volume","274"],["dc.contributor.author","Janssen, P. M. L."],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Prestle, J."],["dc.contributor.author","Lynker, J. C."],["dc.contributor.author","Salfeld, P."],["dc.contributor.author","Just, H."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.date.accessioned","2022-03-01T11:43:46Z"],["dc.date.available","2022-03-01T11:43:46Z"],["dc.date.issued","1998"],["dc.description.abstract","In the intact heart, various triggers induce alterations in gene expression that impact on contractile function. Because changes in gene expression reflect altered protein expression patterns after 12–48 h, we developed a system in which intact twitching cardiac trabeculae can be studied for multiday periods. Right ventricular trabeculae from pentobarbital sodium-anesthetized rabbits were mounted in a sterile, closed muscle chamber. Over the first 48 h, developed force (F dev ) did not significantly change: 102.3 and 98.9% of the initial F dev was observed after 24 and 48 h, respectively ( n = 8). Also, neither diastolic force, time from peak to 50% relaxation (RT 50 ), nor protein synthesis measured by a [ 3 H]leucine incorporation assay changed significantly over time. Contractile response after >48 h to an increase in extracellular calcium concentration (1.8 to 2.5 mM; F dev increased 43.5%, n = 2) or to 1 μM isoproterenol (F dev increased 138.6% and RT 50 decreased 34.9%, n = 2) was similar to those observed in freshly dissected preparations. In conclusion, this system can investigate contractile function of multicellular preparations under well-defined physiological conditions after events that alter gene and consequent protein expression."],["dc.description.abstract","In the intact heart, various triggers induce alterations in gene expression that impact on contractile function. Because changes in gene expression reflect altered protein expression patterns after 12–48 h, we developed a system in which intact twitching cardiac trabeculae can be studied for multiday periods. Right ventricular trabeculae from pentobarbital sodium-anesthetized rabbits were mounted in a sterile, closed muscle chamber. Over the first 48 h, developed force (F dev ) did not significantly change: 102.3 and 98.9% of the initial F dev was observed after 24 and 48 h, respectively ( n = 8). Also, neither diastolic force, time from peak to 50% relaxation (RT 50 ), nor protein synthesis measured by a [ 3 H]leucine incorporation assay changed significantly over time. Contractile response after >48 h to an increase in extracellular calcium concentration (1.8 to 2.5 mM; F dev increased 43.5%, n = 2) or to 1 μM isoproterenol (F dev increased 138.6% and RT 50 decreased 34.9%, n = 2) was similar to those observed in freshly dissected preparations. In conclusion, this system can investigate contractile function of multicellular preparations under well-defined physiological conditions after events that alter gene and consequent protein expression."],["dc.identifier.doi","10.1152/ajpheart.1998.274.5.H1481"],["dc.identifier.gro","3144550"],["dc.identifier.isi","000073514200009"],["dc.identifier.pmid","9612353"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/102837"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Physiological Soc"],["dc.relation.eissn","1522-1539"],["dc.relation.issn","0363-6135"],["dc.title","The trabecula culture system: a novel technique to study contractile parameters over a multiday time period"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","99"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","107"],["dc.bibliographiccitation.volume","47"],["dc.contributor.author","Janssen, P. M. L."],["dc.contributor.author","Zeitz, Oliver"],["dc.contributor.author","Keweloh, B."],["dc.contributor.author","Siegel, U"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Barckhausen, P"],["dc.contributor.author","Pieske, Burkert"],["dc.contributor.author","Prestle, J."],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.date.accessioned","2021-06-01T10:50:03Z"],["dc.date.available","2021-06-01T10:50:03Z"],["dc.date.issued","2000"],["dc.description.abstract","Objective:The immunosuppressive drug Cyclosporine A (CsA) is a key substance in pharmacological therapy following solid organ transplantation and has been suggested to prevent cardiac hypertrophy. We investigated the direct effects of CsA on myocardial function, because these are largely unknown. Methods: In multicellular cardiac muscle preparations from end-stage failing and non-failing human hearts as well as from non-failing rabbit hearts we investigated the effects of CsA on contractile performance, sarcoplasmic reticulum (SR) Ca2+-load, cytosolic calcium transients, calcium sensitivity of the myofilaments, and myocardial oxygen consumption. Results: In failing human muscle preparations there was a concentration dependent decrease in contractile force; the maximal effect amounted to 55.6+/-6.4% of control while EC50 was reached at 1.0+/-0.3 nM (n=6). These concentrations are at and even below the therapeutic plasma levels. CsA decreased the aequorin light signal in human failing trabeculae to 71.5+/-5.9% (n=5), indicating decreased calcium transients. Estimation of the SR calcium load via measurement of rapid cooling contractures revealed a decrease to 84.4+/-6.5% in failing human preparations (n=6). Measurements of both decreased SR calcium load and force development in presence of CsA were also observed in four non-failing human muscle preparations. In rabbit muscle preparations (n=8), developed force decreased to 50.2+/-7.7% (n=8, EC50: 1.9+/-0.4 nM) and rapid cooling contractures to 74.0+/-7.4% of control at 100 nmol/l CsA. No direct effects were observed on myofilament calcium sensitivity nor on maximal force development of permeabilized preparations from the rabbit (n=7). Oxygen consumption measurements showed that CsA decreased the economy of contraction to 76.4+/-7.9% in rabbit preparations (n=8). Conclusions: CsA causes a direct cardio-depressive effect at clinically relevant concentrations, most likely due to altered handling of Ca2+ by the SR. (C) 2000 Elsevier Science B.V. All rights reserved."],["dc.identifier.doi","10.1016/S0008-6363(00)00052-3"],["dc.identifier.gro","3144378"],["dc.identifier.isi","000088204100014"],["dc.identifier.pmid","10869535"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86509"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0008-6363"],["dc.title","Influence of cyclosporine A on contractile function, calcium handling, and energetics in isolated human and rabbit myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]