2022
Gene 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
2017
Protein Phosphatase Inhibitor-1 Gene Therapy in a Swine Model of Nonischemic Heart Failure
Watanabe S, Ishikawa K, Fish K, Oh JG, Motloch LJ, Kohlbrenner E, Lee P, Xie C, Lee A, Liang L, Kho C, Leonardson L, McIntyre M, Wilson S, Samulski RJ, Kranias EG, Weber T, Akar FG, Hajjar RJ. Protein Phosphatase Inhibitor-1 Gene Therapy in a Swine Model of Nonischemic Heart Failure. Journal Of The American College Of Cardiology 2017, 70: 1744-1756. PMID: 28958332, PMCID: PMC5807083, DOI: 10.1016/j.jacc.2017.08.013.Peer-Reviewed Original ResearchConceptsNonischemic heart failureHeart failureEjection fractionIntracoronary deliveryTherapeutic efficacyLeft ventricular end-diastolic pressureDp/dt maximumLeft ventricular ejection fractionVentricular end-diastolic pressureVolume overload heart failureAdverse electrical remodelingIschemic heart failureVentricular ejection fractionVentricular volume indexAtrial ejection fractionEnd-diastolic pressureSevere mitral regurgitationCellular immune responsesCalcium transient amplitudeLarge animal modelGene therapyActive inhibitor-1Improved contractilityInhibitor-1 geneCardiac dysfunction
2014
Cardiac I-1c Overexpression With Reengineered AAV Improves Cardiac Function in Swine Ischemic Heart Failure
Ishikawa K, Fish KM, Tilemann L, Rapti K, Aguero J, Santos-Gallego CG, Lee A, Karakikes I, Xie C, Akar FG, Shimada YJ, Gwathmey JK, Asokan A, McPhee S, Samulski J, Samulski RJ, Sigg DC, Weber T, Kranias EG, Hajjar RJ. Cardiac I-1c Overexpression With Reengineered AAV Improves Cardiac Function in Swine Ischemic Heart Failure. Molecular Therapy 2014, 22: 2038-2045. PMID: 25023328, PMCID: PMC4429688, DOI: 10.1038/mt.2014.127.Peer-Reviewed Original ResearchConceptsIschemic heart failureHigh-dose groupHeart failureCardiac functionLarge anterior myocardial infarctionLeft ventricular ejection fractionPreload recruitable stroke workChronic heart failureAdvanced heart failureLow-dose groupVentricular ejection fractionAnterior myocardial infarctionActive inhibitor-1Ejection fractionIntracoronary injectionSaline groupContractility indexMyocardial infarctionPressure-volume analysisStroke volumeStroke workCardiac performanceHemodynamic parametersCardiovascular systemCardiac gene therapy