2024
Quantitative Assessment of Mitochondrial Morphology and Electrophysiological Function in the Diabetic Heart
Cacheux M, Rudokas M, Tieu A, Rizk J, Hummel M, Akar F. Quantitative Assessment of Mitochondrial Morphology and Electrophysiological Function in the Diabetic Heart. Methods In Molecular Biology 2024, 2803: 75-86. PMID: 38676886, DOI: 10.1007/978-1-0716-3846-0_6.Peer-Reviewed Original ResearchConceptsMitochondrial shapeMitochondrial networkMitochondrial architectureSubcellular localizationMitochondrial morphologyDiabetic heartOxidative phosphorylationATP synthesisAction potentialsSarcolemmal ion channelsExcitation-contraction couplingFission eventsOptical action potentialsExcitation-contractionCardiac myocytesElectrophysiological properties
2021
Right predominant electrical remodeling in a pure model of pulmonary hypertension promotes reentrant arrhythmias
Strauss B, Bisserier M, Obus E, Katz MG, Fargnoli A, Cacheux M, Akar JG, Hummel JP, Hadri L, Sassi Y, Akar FG. Right predominant electrical remodeling in a pure model of pulmonary hypertension promotes reentrant arrhythmias. Heart Rhythm 2021, 19: 113-124. PMID: 34563688, PMCID: PMC8742785, DOI: 10.1016/j.hrthm.2021.09.021.Peer-Reviewed Original ResearchConceptsPulmonary arterial hypertensionVT/VFExtrapulmonary toxicityPN ratsVentricular tachycardia/fibrillationCardiac magnetic resonance imagingRight ventricular hypertrophySprague-Dawley ratsMultiple reentrant circuitsConnexin 43 expressionMagnetic resonance imagingConnexin 43 phosphorylationRV activationArterial hypertensionMonocrotaline modelVentricular hypertrophyLeft pneumonectomyElectrical remodelingMyocardial fibrosisConduction slowingSevere formAP durationArrhythmic vulnerabilityReentrant circuitAP alternans
2019
Renewal Theory as a Universal Quantitative Framework to Characterize Phase Singularity Regeneration in Mammalian Cardiac Fibrillation
Dharmaprani D, Schopp M, Kuklik P, Chapman D, Lahiri A, Dykes L, Xiong F, Aguilar M, Strauss B, Mitchell L, Pope K, Meyer C, Willems S, Akar FG, Nattel S, McGavigan AD, Ganesan AN. Renewal Theory as a Universal Quantitative Framework to Characterize Phase Singularity Regeneration in Mammalian Cardiac Fibrillation. Circulation Arrhythmia And Electrophysiology 2019, 12: e007569. PMID: 31813270, DOI: 10.1161/circep.119.007569.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAtrial FibrillationBiological EvolutionComputer SimulationDisease Models, AnimalHeart Conduction SystemHeart RateHumansModels, CardiovascularMulticenter Studies as TopicObservational Studies as TopicRatsReproducibility of ResultsSheep, DomesticStochastic ProcessesTime FactorsVentricular FibrillationConceptsPoisson renewal processRenewal theoryRenewal processPhase singularityMaximum entropy theoryExponential probability distribution functionProbability distribution functionFormation/destructionConstant rate parametersEntropy theoryInterevent timesDistribution functionExponential distributionRotational events
2018
Optical Action Potential Mapping in Acute Models of Ischemia–Reperfusion Injury: Probing the Arrhythmogenic Role of the Mitochondrial Translocator Protein
Ilkan Z, Strauss B, Campana C, Akar FG. Optical Action Potential Mapping in Acute Models of Ischemia–Reperfusion Injury: Probing the Arrhythmogenic Role of the Mitochondrial Translocator Protein. Methods In Molecular Biology 2018, 1816: 133-143. PMID: 29987816, DOI: 10.1007/978-1-4939-8597-5_10.Peer-Reviewed Original ResearchConceptsOptical action potential mappingIschemia-reperfusion injuryTranslocator proteinPost-ischemic arrhythmiasIonotropic propertiesPostischemic arrhythmiasR injuryHypertensive ratsAcute modelArrhythmogenic roleElectrophysiological substrateElectrophysiological propertiesArrhythmia mechanismsPharmacological inhibitionIntact heartInjuryTSPO ligandsMitochondrial translocator proteinArrhythmiasTSPO geneHeartPatientsRatsQuantitative assessmentIncidence
2015
The Classically Cardioprotective Agent Diazoxide Elicits Arrhythmias in Type 2 Diabetes Mellitus
Xie C, Hu J, Motloch LJ, Karam BS, Akar FG. The Classically Cardioprotective Agent Diazoxide Elicits Arrhythmias in Type 2 Diabetes Mellitus. Journal Of The American College Of Cardiology 2015, 66: 1144-1156. PMID: 26337994, PMCID: PMC4560843, DOI: 10.1016/j.jacc.2015.06.1329.Peer-Reviewed Original ResearchConceptsAction potential durationVentricular tachyarrhythmiasT2DM heartsIschemia-induced ventricular tachyarrhythmiasOptical action potential mappingType 2 diabetes mellitusAdenosine triphosphate-sensitive potassium channelsMitochondrial adenosine triphosphate-sensitive potassium channelsTriphosphate-sensitive potassium channelsLow-dose diazoxideFree fatty acid levelsIncidence of arrhythmiasNormal Sprague-Dawley ratsSprague-Dawley ratsOnset of arrhythmiasMessenger ribonucleic acid expressionFatty acid levelsRibonucleic acid expressionAPD adaptationElicit arrhythmiasUntreated T2DMIschemic eventsDiabetes mellitusDiabetic patientsIschemic challenge
2014
Effect of bortezomib on the efficacy of AAV9.SERCA2a treatment to preserve cardiac function in a rat pressure-overload model of heart failure
Chaanine A, Nonnenmacher M, Kohlbrenner E, Jin D, Kovacic J, Akar F, Hajjar R, Weber T. Effect of bortezomib on the efficacy of AAV9.SERCA2a treatment to preserve cardiac function in a rat pressure-overload model of heart failure. Gene Therapy 2014, 21: 379-386. PMID: 24572786, PMCID: PMC3976435, DOI: 10.1038/gt.2014.7.Peer-Reviewed Original ResearchConceptsHeart failureCardiac functionRodent heart failure modelsRat cardiomyocytesHeart failure modelPressure overload modelEffect of bortezomibProteasome inhibitor bortezomibNeonatal rat cardiomyocytesAdult rat cardiomyocytesWestern blot analysisSERCA2a proteinPressure-volume analysisSERCA2a levelsBortezomib treatmentConcurrent treatmentSERCA2a mRNAInhibitor bortezomibBortezomibHeart samplesHuman SERCA2aSerotype 1Proteasome inhibitorsAAV serotypes 1Proteasome inhibition
2011
Biophysical properties and functional consequences of reactive oxygen species (ROS)‐induced ROS release in intact myocardium
Biary N, Xie C, Kauffman J, Akar FG. Biophysical properties and functional consequences of reactive oxygen species (ROS)‐induced ROS release in intact myocardium. The Journal Of Physiology 2011, 589: 5167-5179. PMID: 21825030, PMCID: PMC3225672, DOI: 10.1113/jphysiol.2011.214239.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntioxidantsArrhythmias, CardiacCyclosporineDiazepamEthidiumFluorescenceFluorescent DyesHydrogen PeroxideIn Vitro TechniquesIntracellular MembranesMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMyocardiumOrganometallic CompoundsOxidantsOxidative StressRatsSalicylatesSuperoxidesVoltage-Dependent Anion ChannelsConceptsIncidence of arrhythmiasIntact myocardiumOxidative stressMitochondrial permeability transition poreReactive oxygen speciesSustained ventricular tachycardiaROS releaseExposure of heartsGlobal oxidative stressPerfusion of heartsSuperoxide dismutase/catalase mimetic EUK-134Functional consequencesOS protocolArrhythmia scoreAcute modelDihydroethidium fluorescenceUntreated heartsVentricular tachycardiaVentricular fibrillationOxygen speciesArrhythmic consequencesElevated ROS levelsRat heartEUK-134PerfusionDisruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis
Smeele KM, Southworth R, Wu R, Xie C, Nederlof R, Warley A, Nelson JK, van Horssen P, van den Wijngaard JP, Heikkinen S, Laakso M, Koeman A, Siebes M, Eerbeek O, Akar FG, Ardehali H, Hollmann MW, Zuurbier CJ. Disruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis. Circulation Research 2011, 108: 1165-1169. PMID: 21527739, DOI: 10.1161/circresaha.111.244962.Peer-Reviewed Original ResearchConceptsIschemic preconditioningWild-type heartsCardiac functionProtective effectHKII levelsBaseline cardiac functionIschemia-reperfusion injuryNormal cardiac functionMitochondrial permeability transition openingContractile impairmentReperfusion injuryAcute reductionCardiac necrosisMyocardial functionGlycolytic enzymes hexokinaseCardiac contractionMild mitochondrial uncouplingMembrane depolarizationMitochondrial membrane depolarizationHKIIMitochondrial hexokinaseControl peptideHeartPreconditioningTissue disruption
2010
A brighter side of ROS revealed by selective activation of β‐adrenergic receptor subtypes
Biary N, Akar FG. A brighter side of ROS revealed by selective activation of β‐adrenergic receptor subtypes. The Journal Of Physiology 2010, 588: 2973-2974. PMID: 20710039, PMCID: PMC2956937, DOI: 10.1113/jphysiol.2010.195743.Commentaries, Editorials and LettersAdrenergic beta-1 Receptor AgonistsAdrenergic beta-2 Receptor AgonistsAnimalsGTP-Binding Protein alpha Subunits, Gi-GoHomeostasisHumansMyocytes, CardiacNitric OxideNitric Oxide Synthase Type IIIOxygenRatsReactive Oxygen SpeciesReceptors, Adrenergic, beta-1Receptors, Adrenergic, beta-2Signal TransductionOptical imaging of mitochondrial function uncovers actively propagating waves of mitochondrial membrane potential collapse across intact heart
Lyon AR, Joudrey PJ, Jin D, Nass RD, Aon MA, O'Rourke B, Akar FG. Optical imaging of mitochondrial function uncovers actively propagating waves of mitochondrial membrane potential collapse across intact heart. Journal Of Molecular And Cellular Cardiology 2010, 49: 565-575. PMID: 20624394, PMCID: PMC3081287, DOI: 10.1016/j.yjmcc.2010.07.002.Peer-Reviewed Original ResearchAltered Spatiotemporal Dynamics of the Mitochondrial Membrane Potential in the Hypertrophied Heart
Jin H, Nass RD, Joudrey PJ, Lyon AR, Chemaly ER, Rapti K, Akar FG. Altered Spatiotemporal Dynamics of the Mitochondrial Membrane Potential in the Hypertrophied Heart. Biophysical Journal 2010, 98: 2063-2071. PMID: 20483313, PMCID: PMC2872265, DOI: 10.1016/j.bpj.2010.01.045.Peer-Reviewed Original ResearchUltrastructure and Regulation of Lateralized Connexin43 in the Failing Heart
Hesketh GG, Shah MH, Halperin VL, Cooke CA, Akar FG, Yen TE, Kass DA, Machamer CE, Van Eyk JE, Tomaselli GF. Ultrastructure and Regulation of Lateralized Connexin43 in the Failing Heart. Circulation Research 2010, 106: 1153-1163. PMID: 20167932, PMCID: PMC2896878, DOI: 10.1161/circresaha.108.182147.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyConnexin 43Disease Models, AnimalDogsGap JunctionsHeart FailureHeart VentriclesHeLa CellsHumansMembrane MicrodomainsMicroscopy, ConfocalMicroscopy, Electron, TransmissionMicrotubule-Associated ProteinsMyocardiumPhosphorylationRatsRats, Sprague-DawleyRecombinant Fusion ProteinsTransfectionConceptsGFP-LC3Gap junctionsLateral membranesDistinct phosphorylated formsGap junction turnoverGap junction internalizationForm of LC3Internalized gap junctionsGap junction proteinJunction turnoverSubcellular locationBiochemical regulationCellular pathwaysMultilamellar membrane structuresEndogenous Cx43Phosphorylated formNeonatal rat ventricular myocytesHeLa cellsIntracellular Cx43Membrane structureJunction proteinsCx43ProteinPotential therapeutic implicationsConnexin43
2009
Mechanoelectrical remodeling and arrhythmias during progression of hypertrophy
Jin H, Chemaly ER, Lee A, Kho C, Hadri L, Hajjar RJ, Akar FG. Mechanoelectrical remodeling and arrhythmias during progression of hypertrophy. The FASEB Journal 2009, 24: 451-463. PMID: 19825979, PMCID: PMC2812033, DOI: 10.1096/fj.09-136622.Peer-Reviewed Original ResearchConceptsConduction delayLeft ventricular mechanical dysfunctionEnd-stage heart failureTissue levelsVentricular mechanical dysfunctionIncidence of arrhythmiasSudden cardiac deathZO-1Pressure overload hypertrophyAction potential prolongationProgression of hypertrophyDisease developmentLV dysfunctionCardiac deathDephosphorylation of Cx43Heart failureAortic bandingElectrical remodelingVentricular tachycardiaMechanical dysfunctionOverload hypertrophyElectrophysiological changesRat modelPotential prolongationProtein ZO-1
2004
Functional Integration of Electrically Active Cardiac Derivatives From Genetically Engineered Human Embryonic Stem Cells With Quiescent Recipient Ventricular Cardiomyocytes
Xue T, Cho HC, Akar FG, Tsang SY, Jones SP, Marbán E, Tomaselli GF, Li RA. Functional Integration of Electrically Active Cardiac Derivatives From Genetically Engineered Human Embryonic Stem Cells With Quiescent Recipient Ventricular Cardiomyocytes. Circulation 2004, 111: 11-20. PMID: 15611367, DOI: 10.1161/01.cir.0000151313.18547.a2.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdrenergic beta-AgonistsAnimalsCell DifferentiationCell FusionCells, CulturedDefective VirusesElectrophysiologyFemaleGenes, ReporterGenetic VectorsGiant CellsGreen Fluorescent ProteinsGuinea PigsHeartHeart Conduction SystemHeart VentriclesHIV-1HumansIsoproterenolLidocaineMiceMyocardial ContractionMyocytes, CardiacOrgan Culture TechniquesPericardiumPluripotent Stem CellsPyrimidinesRatsTransduction, GeneticConceptsVentricular cardiomyocytesCardiac impulse generationBeta-adrenergic agonist isoproterenolGuinea pig heartsSite of injectionStem cellsHuman embryonic stem cellsCell-based therapiesContractile activityAgonist isoproterenolPharmacological agentsVentricular myocardiumLeft ventricleEx vivoDonor cardiomyocytesPig heartsHuman cardiomyocytesRecombinant lentivirusMembrane depolarizationCardiomyocytesFunctional syncytiumImpulse generationEmbryonic stem cellsMyocardiumEpicardial surface