Mason, Fleur E.

[["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Mason, Fleur E."],["dc.contributor.author","Pronto, Julius Ryan D."],["dc.contributor.author","Alhussini, Khaled"],["dc.contributor.author","Maack, Christoph"],["dc.contributor.author","Voigt, Niels"],["dc.date.accessioned","2021-04-14T08:30:49Z"],["dc.date.available","2021-04-14T08:30:49Z"],["dc.date.issued","2020"],["dc.description.abstract","The molecular mechanisms underlying atrial fibrillation (AF), the most common form of arrhythmia, are poorly understood and therefore target-specific treatment options remain an unmet clinical need. Excitation–contraction coupling in cardiac myocytes requires high amounts of adenosine triphosphate (ATP), which is replenished by oxidative phosphorylation in mitochondria. Calcium (Ca2+) is a key regulator of mitochondrial function by stimulating the Krebs cycle, which produces nicotinamide adenine dinucleotide for ATP production at the electron transport chain and nicotinamide adenine dinucleotide phosphate for the elimination of reactive oxygen species (ROS). While it is now well established that mitochondrial dysfunction plays an important role in the pathophysiology of heart failure, this has been less investigated in atrial myocytes in AF. Considering the high prevalence of AF, investigating the role of mitochondria in this disease may guide the path towards new therapeutic targets. In this review, we discuss the importance of mitochondrial Ca2+ handling in regulating ATP production and mitochondrial ROS emission and how alterations, particularly in these aspects of mitochondrial activity, may play a role in AF. In addition to describing research advances, we highlight areas in which further studies are required to elucidate the role of mitochondria in AF."],["dc.identifier.doi","10.1007/s00395-020-00827-7"],["dc.identifier.pmid","33258071"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83381"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/137"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/379"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A13: Bedeutung einer gestörten zytosolischen Calciumpufferung bei der atrialen Arrhythmogenese bei Patienten mit Herzinsuffizienz (HF)"],["dc.relation.eissn","1435-1803"],["dc.relation.issn","0300-8428"],["dc.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.rights","CC BY 4.0"],["dc.title","Cellular and mitochondrial mechanisms of atrial fibrillation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","overview_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4816"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.affiliation","Wagner, Michael; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany, michael_wagner@tu-dresden.de\t\t \r\n\t\t Klinik für Innere Medizin und Kardiologie, Dresden Heart Center, Dresden University of Technology, 01307 Dresden, Germany, michael_wagner@tu-dresden.de"],["dc.contributor.affiliation","Sadek, Mirna S.; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany, mirna.sadeks@gmail.com"],["dc.contributor.affiliation","Dybkova, Nataliya; \t\t \r\n\t\t Clinic for Cardiology & Pneumology, University of Göttingen, 37075 Göttingen, Germany, ndybkov@med.uni-goettingen.de\t\t \r\n\t\t DZHK (German Centre for Cardiovascular Research), 10785 Berlin, Germany, ndybkov@med.uni-goettingen.de"],["dc.contributor.affiliation","Mason, Fleur E.; \t\t \r\n\t\t Clinic for Cardiology & Pneumology, University of Göttingen, 37075 Göttingen, Germany, fleur.mason@med.uni-goettingen.de\t\t \r\n\t\t DZHK (German Centre for Cardiovascular Research), 10785 Berlin, Germany, fleur.mason@med.uni-goettingen.de"],["dc.contributor.affiliation","Klehr, Johann; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany, johann.klehr@tu-dresden.de"],["dc.contributor.affiliation","Firneburg, Rebecca; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany, rebecca.firneburg@tu-dresden.de"],["dc.contributor.affiliation","Cachorro, Eleder; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany, eleder.cachorro_puente@tu-dresden.de"],["dc.contributor.affiliation","Richter, Kurt; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany, kurt.richter@outlook.de\t\t \r\n\t\t Klinik für Innere Medizin und Kardiologie, Dresden Heart Center, Dresden University of Technology, 01307 Dresden, Germany, kurt.richter@outlook.de"],["dc.contributor.affiliation","Klapproth, Erik; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany, erik.klapproth@tu-dresden.de"],["dc.contributor.affiliation","Kuenzel, Stephan R.; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany, Stephan.kuenzel@tu-dresden.de"],["dc.contributor.affiliation","Lorenz, Kristina; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Julius-Maximilians-Universität Würzburg, 97078 Würzburg, Germany, lorenz@toxi.uni-wuerzburg.de\t\t \r\n\t\t Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., 44139 Dortmund, Germany, lorenz@toxi.uni-wuerzburg.de"],["dc.contributor.affiliation","Heijman, Jordi; \t\t \r\n\t\t Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine, and Life Sciences, Maastricht University, 6200 MD Maastricht, The Netherlands, Jordi.heijman@maastrichtuniversity.nl"],["dc.contributor.affiliation","Dobrev, Dobromir; \t\t \r\n\t\t Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, 45147 Essen, Germany, Dobromir.dobrev@uk-essen.de\t\t \r\n\t\t Montréal Heart Institute, Research Center, University de Montréal, Montréal, QC H1T 1C8, Canada, Dobromir.dobrev@uk-essen.de\t\t \r\n\t\t Department of Molecular Physiology Biophysics, Baylor College of Medicine, Houston, TX 77030, USA, Dobromir.dobrev@uk-essen.de"],["dc.contributor.affiliation","El-Armouche, Ali; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany, ali.el-armouche@tu-dresden.de"],["dc.contributor.affiliation","Sossalla, Samuel; \t\t \r\n\t\t Clinic for Cardiology & Pneumology, University of Göttingen, 37075 Göttingen, Germany, samuel.sossalla@ukr.de\t\t \r\n\t\t DZHK (German Centre for Cardiovascular Research), 10785 Berlin, Germany, samuel.sossalla@ukr.de\t\t \r\n\t\t Department of Internal Medicine II, University Hospital Regensburg, 93042 Regensburg, Germany, samuel.sossalla@ukr.de"],["dc.contributor.affiliation","Kämmerer, Susanne; \t\t \r\n\t\t Department of Pharmacology and Toxicology, Dresden University of Technology, 01307 Dresden, Germany, susanne.kaemmerer@tu-dresden.de"],["dc.contributor.author","Wagner, Michael"],["dc.contributor.author","Sadek, Mirna S."],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Mason, Fleur E."],["dc.contributor.author","Klehr, Johann"],["dc.contributor.author","Firneburg, Rebecca"],["dc.contributor.author","Cachorro, Eleder"],["dc.contributor.author","Richter, Kurt"],["dc.contributor.author","Klapproth, Erik"],["dc.contributor.author","Kämmerer, Susanne"],["dc.contributor.author","Kuenzel, Stephan R."],["dc.contributor.author","Lorenz, Kristina"],["dc.contributor.author","Heijman, Jordi"],["dc.contributor.author","Dobrev, Dobromir"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2021-06-01T09:42:36Z"],["dc.date.available","2021-06-01T09:42:36Z"],["dc.date.issued","2021"],["dc.date.updated","2022-11-11T13:15:11Z"],["dc.description.abstract","Background: Phosphodiesterases (PDE) critically regulate myocardial cAMP and cGMP levels. PDE2 is stimulated by cGMP to hydrolyze cAMP, mediating a negative crosstalk between both pathways. PDE2 upregulation in heart failure contributes to desensitization to β-adrenergic overstimulation. After isoprenaline (ISO) injections, PDE2 overexpressing mice (PDE2 OE) were protected against ventricular arrhythmia. Here, we investigate the mechanisms underlying the effects of PDE2 OE on susceptibility to arrhythmias. Methods: Cellular arrhythmia, ion currents, and Ca2+-sparks were assessed in ventricular cardiomyocytes from PDE2 OE and WT littermates. Results: Under basal conditions, action potential (AP) morphology were similar in PDE2 OE and WT. ISO stimulation significantly increased the incidence of afterdepolarizations and spontaneous APs in WT, which was markedly reduced in PDE2 OE. The ISO-induced increase in ICaL seen in WT was prevented in PDE2 OE. Moreover, the ISO-induced, Epac- and CaMKII-dependent increase in INaL and Ca2+-spark frequency was blunted in PDE2 OE, while the effect of direct Epac activation was similar in both groups. Finally, PDE2 inhibition facilitated arrhythmic events in ex vivo perfused WT hearts after reperfusion injury. Conclusion: Higher PDE2 abundance protects against ISO-induced cardiac arrhythmia by preventing the Epac- and CaMKII-mediated increases of cellular triggers. Thus, activating myocardial PDE2 may represent a novel intracellular anti-arrhythmic therapeutic strategy in HF."],["dc.description.sponsorship","German Research Foundation"],["dc.identifier.doi","10.3390/ijms22094816"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85300"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.publisher","MDPI"],["dc.relation.eissn","1422-0067"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Cellular Mechanisms of the Anti-Arrhythmic Effect of Cardiac PDE2 Overexpression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]