2022
A 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
2021
Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation
Raad N, Bittihn P, Cacheux M, Jeong D, Ilkan Z, Ceholski D, Kohlbrenner E, Zhang L, Cai CL, Kranias EG, Hajjar RJ, Stillitano F, Akar FG. Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation. Circulation 2021, 144: 441-454. PMID: 34024116, PMCID: PMC8456417, DOI: 10.1161/circulationaha.119.043502.Peer-Reviewed Original ResearchConceptsHuman PLNRapid pacingInterventricular activation delayHumanized mouse modelAction potential prolongationLocal conduction blockSteep repolarization gradientsArrhythmogenic featuresMacroreentrant circuitHemodynamic changesElectric remodelingElectrophysiological remodelingRight ventricleVentricular tachycardiaPotential prolongationSudden deathConduction blockMouse modelAdult knockArrhythmia susceptibilityAdrenergic stimulationStructural remodelingArrhythmogenic phenotypeArrhythmia mechanismsRegulatory protein phospholamban