2024
Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction
Rudokas M, McKay M, Toksoy Z, Eisen J, Bögner M, Young L, Akar F. Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction. Cardiovascular Diabetology 2024, 23: 261. PMID: 39026280, PMCID: PMC11264840, DOI: 10.1186/s12933-024-02357-1.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesMitochondrial network remodelingDamaged mitochondrial DNAEfficiency of oxidative phosphorylationImpaired ATP productionMitochondrial ultrastructural alterationsCardiac functionDiabetic heartCellular energy metabolismProduction of reactive oxygen speciesMitochondrial DNAMitochondrial networkMitochondrial fissionExcessive production of reactive oxygen speciesOxidative phosphorylationATP productionResponse to ischemic insultGlobal cardiac functionCell deathOverall cardiac functionCardiac ischemic injuryResponse to injuryCardiac mitochondriaIrreversible cell deathMitochondriaPO-05-130 DEMONSTRATING THE IMPACT OF LESION ORIENTATION ON ABLATION EFFICIENCY IN AN ANISOTROPIC MODEL OF PERSISTENT ATRIAL FIBRILLATION
Reiss M, Mulimani M, Luther S, Akar J, Rappel W, Akar F, Hummel J. PO-05-130 DEMONSTRATING THE IMPACT OF LESION ORIENTATION ON ABLATION EFFICIENCY IN AN ANISOTROPIC MODEL OF PERSISTENT ATRIAL FIBRILLATION. Heart Rhythm 2024, 21: s535. DOI: 10.1016/j.hrthm.2024.03.1365.Peer-Reviewed Original ResearchMP-470551-008 ATRIAL FIBRILLATION IN MICE WITH AMPK DELETION IS MEDIATED BY TRIGGERED ACTIVITY FROM THE PULMONARY VEIN JUNCTION
Cacheux M, Velasco J, Wu X, Akar J, Young L, Akar F. MP-470551-008 ATRIAL FIBRILLATION IN MICE WITH AMPK DELETION IS MEDIATED BY TRIGGERED ACTIVITY FROM THE PULMONARY VEIN JUNCTION. Heart Rhythm 2024, 21: s107. DOI: 10.1016/j.hrthm.2024.03.1772.Peer-Reviewed Original ResearchPO-05-168 CARDIOMYOCYTE STIM1 EXPRESSION REGULATES POST-ISCHEMIC CARDIAC FUNCTION BY CONTROLLING METABOLIC PROCESSES AND MITOCHONDRIAL ULTRASTRUCTURE
Cacheux M, Wu X, Akar F. PO-05-168 CARDIOMYOCYTE STIM1 EXPRESSION REGULATES POST-ISCHEMIC CARDIAC FUNCTION BY CONTROLLING METABOLIC PROCESSES AND MITOCHONDRIAL ULTRASTRUCTURE. Heart Rhythm 2024, 21: s570-s571. DOI: 10.1016/j.hrthm.2024.03.1439.Peer-Reviewed Original ResearchExtracellular Cyclic AMP Suppresses Pulmonary Arterial Hypertension-induced Ventricular Arrhythmias
Imani S, Strauss B, Obus E, Cacheux M, Hadri L, Akar F, Sassi Y. Extracellular Cyclic AMP Suppresses Pulmonary Arterial Hypertension-induced Ventricular Arrhythmias. 2024, a4051-a4051. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4051.Peer-Reviewed Original ResearchQuantitative 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 propertiesA new year’s resolution to resolve atrial fibrillation: Resolvin D1 emerges as a powerful target against post-MI atrial remodelling
Velasco J, Akar F. A new year’s resolution to resolve atrial fibrillation: Resolvin D1 emerges as a powerful target against post-MI atrial remodelling. Cardiovascular Research 2024, 120: 329-330. PMID: 38387430, PMCID: PMC10981522, DOI: 10.1093/cvr/cvae039.Peer-Reviewed Original ResearchTop Stories: Mitochondrial origin of inherited cardiac arrhythmias
Akar F, Maack C. Top Stories: Mitochondrial origin of inherited cardiac arrhythmias. Heart Rhythm 2024, 21: 235-236. PMID: 38296456, PMCID: PMC10857749, DOI: 10.1016/j.hrthm.2023.10.020.Peer-Reviewed Original Research
2023
Chronic diastolic stretch unmasks conduction defects in an in vitro model of arrhythmogenic cardiomyopathy
Ng R, Gokhan I, Stankey P, Akar F, Campbell S. Chronic diastolic stretch unmasks conduction defects in an in vitro model of arrhythmogenic cardiomyopathy. AJP Heart And Circulatory Physiology 2023, 325: h1373-h1385. PMID: 37830983, PMCID: PMC10977872, DOI: 10.1152/ajpheart.00709.2022.Peer-Reviewed Original ResearchArrhythmogenic cardiomyopathyDiastolic stretchConduction deficitsConduction velocityIntensity of exerciseAction potential parametersDifferent time pointsDisease progressionHigh afterloadContractile functionHemodynamic parametersProgressive disorderUnderlying pathomechanismsArrhythmia vulnerabilityConduction defectsPhysiological shorteningHeart tissueConnexin 43Time pointsERK signalingCardiomyopathyLysosome activityCardiac cycleDesmosomal proteinsExerciseA unifying mechanism for the initiation of torsade de pointes: blurring the distinction between trigger and substrate
McKay M, Akar F. A unifying mechanism for the initiation of torsade de pointes: blurring the distinction between trigger and substrate. Cardiovascular Research 2023, 119: 333-335. PMID: 36869679, DOI: 10.1093/cvr/cvad033.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsRole of AMPK pathway inactivation in high fat diet related cardiac electrophysiological remodeling
Rudokas M, Cacheux M, Wu X, Hummel M, Young L, Akar F. Role of AMPK pathway inactivation in high fat diet related cardiac electrophysiological remodeling. Biophysical Journal 2023, 122: 380a-381a. DOI: 10.1016/j.bpj.2022.11.2089.Peer-Reviewed Original Research
2022
Humanized Dsp ACM Mouse Model Displays Stress-Induced Cardiac Electrical and Structural Phenotypes
Stevens TL, Manring HR, Wallace MJ, Argall A, Dew T, Papaioannou P, Antwi-Boasiako S, Xu X, Campbell SG, Akar FG, Borzok MA, Hund TJ, Mohler PJ, Koenig SN, El Refaey M. Humanized Dsp ACM Mouse Model Displays Stress-Induced Cardiac Electrical and Structural Phenotypes. Cells 2022, 11: 3049. PMID: 36231013, PMCID: PMC9562631, DOI: 10.3390/cells11193049.Peer-Reviewed Original ResearchConceptsArrhythmogenic cardiomyopathyMouse modelStructural phenotypesFibro-fatty infiltrationFirst mouse modelHeart failureChamber dilationVentricular arrhythmiasPressure overloadArrhythmic eventsCardiac performanceCardiac stressSudden deathCardiovascular stressInherited disorderG variantConnexin 43MiceDesmosomal genesReduced expressionExternal stressorsACM familyDisease developmentMurine equivalentIncomplete penetranceMetabolic Regulation of Mitochondrial Dynamics and Cardiac Function
Rudokas M, Cacheux M, Akar F. Metabolic Regulation of Mitochondrial Dynamics and Cardiac Function. 2022, 197-211. DOI: 10.1007/978-3-031-08309-9_6.BooksMitochondrial dynamicsNormal embryonic developmentMitochondrial dynamics proteinsDynamic organellesMitochondrial networkMitochondrial fusionDynamic proteinsEmbryonic developmentFragmented mitochondriaKey proteinsKey regulatorFunctional importanceMetabolic regulationAltered regulationMitochondriaFission eventsFundamental processesProteinCardiac mitochondriaFission resultsRegulationMorphological changesRecent advancesOrganellesRegulatorThe inspection paradox: An important consideration in the evaluation of rotor lifetimes in cardiac fibrillation
Jenkins EV, Dharmaprani D, Schopp M, Quah JX, Tiver K, Mitchell L, Xiong F, Aguilar M, Pope K, Akar FG, Roney CH, Niederer SA, Nattel S, Nash MP, Clayton RH, Ganesan AN. The inspection paradox: An important consideration in the evaluation of rotor lifetimes in cardiac fibrillation. Frontiers In Physiology 2022, 13: 920788. PMID: 36148313, PMCID: PMC9486478, DOI: 10.3389/fphys.2022.920788.Peer-Reviewed Original ResearchEditorial: The role of genetics and non-coding RNAs in atrial fibrillation
Novelli V, Akar FG. Editorial: The role of genetics and non-coding RNAs in atrial fibrillation. Frontiers In Cardiovascular Medicine 2022, 9: 997700. PMID: 35990985, PMCID: PMC9382284, DOI: 10.3389/fcvm.2022.997700.Commentaries, Editorials and LettersModern Day Wearables to Evade the Widow-Ghost in Brugada Syndrome From Mythology to Deep-Learning Methodology ∗
Karam CS, Akar FG. Modern Day Wearables to Evade the Widow-Ghost in Brugada Syndrome From Mythology to Deep-Learning Methodology ∗. JACC Clinical Electrophysiology 2022, 8: 1021-1023. PMID: 35981789, DOI: 10.1016/j.jacep.2022.06.017.Commentaries, Editorials and LettersPO-616-05 THE INSPECTION PARADOX: AN IMPORTANT CONSIDERATION IN THE EVALUATION OF ROTOR LIFETIMES IN CARDIAC FIBRILLATION
Jenkins E, Dharmaprani D, Schopp M, Quah J, Tiver K, Xiong F, Aguilar M, Akar F, Roney C, Niederer S, Nattel S, Nash M, Clayton R, Ganesan A. PO-616-05 THE INSPECTION PARADOX: AN IMPORTANT CONSIDERATION IN THE EVALUATION OF ROTOR LIFETIMES IN CARDIAC FIBRILLATION. Heart Rhythm 2022, 19: s112. DOI: 10.1016/j.hrthm.2022.03.801.Peer-Reviewed Original ResearchAtrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation
Su KN, Ma Y, Cacheux M, Ilkan Z, Raad N, Muller GK, Wu X, Guerrera N, Thorn SL, Sinusas AJ, Foretz M, Viollet B, Akar JG, Akar FG, Young LH. Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation. JCI Insight 2022, 7: e141213. PMID: 35451373, PMCID: PMC9089788, DOI: 10.1172/jci.insight.141213.Peer-Reviewed Original ResearchConceptsTranscription factorsKey transcription factorMaster metabolic regulatorIon channel subunitsGap junction proteinTranscriptional reprogrammingAMPK deletionProtein kinaseBiological functionsTranscriptional downregulationMetabolic regulatorChannel subunitsIon channelsAMPK expressionMetabolic stressAtrial fibrillationAMPKJunction proteinsElectrical excitabilityHomeostatic roleStructural remodelingConnexinsAtrial ion channelsRemodelingDownregulationA novel exosome-based therapy for post-MI arrhythmias
Cacheux M, Akar FG. A novel exosome-based therapy for post-MI arrhythmias. European Heart Journal 2022, 43: 2157-2159. PMID: 35325140, DOI: 10.1093/eurheartj/ehac155.Peer-Reviewed Original ResearchGene editing reverses arrhythmia susceptibility in humanized PLN-R14del mice: modelling a European cardiomyopathy with global impact
Dave J, Raad N, Mittal N, Zhang L, Fargnoli A, Oh JG, Savoia ME, Hansen J, Fava M, Yin X, Theofilatos K, Ceholski D, Kohlbrenner E, Jeong D, Wills L, Nonnenmacher M, Haghighi K, Costa KD, Turnbull IC, Mayr M, Cai CL, Kranias EG, Akar FG, Hajjar RJ, Stillitano F. Gene editing reverses arrhythmia susceptibility in humanized PLN-R14del mice: modelling a European cardiomyopathy with global impact. Cardiovascular Research 2022, 118: 3140-3150. PMID: 35191471, PMCID: PMC9732517, DOI: 10.1093/cvr/cvac021.Peer-Reviewed Original ResearchConceptsAdeno-associated virus 9Ventricular tachycardiaCardiac functionStroke volumeHigh arrhythmia burdenSustained ventricular tachycardiaSudden cardiac deathCardiac magnetic resonancePre-symptomatic carriersYoung adult miceWeeks of ageDroplet digital polymerase chain reactionArrhythmia burdenVulnerable myocardiumCardiac deathEjection fractionPreclinical evidenceMalignant arrhythmiasVentricular dilationHumanized miceWT miceCardiac outputPolymerase chain reactionPLN-R14DelAdult mice