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 therapyEffect 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
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