2020
Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy
Toepfer CN, Garfinkel AC, Venturini G, Wakimoto H, Repetti G, Alamo L, Sharma A, Agarwal R, Ewoldt JF, Cloonan P, Letendre J, Lun M, Olivotto I, Colan S, Ashley E, Jacoby D, Michels M, Redwood CS, Watkins HC, Day SM, Staples JF, Padrón R, Chopra A, Ho CY, Chen CS, Pereira AC, Seidman JG, Seidman CE. Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy. Circulation 2020, 141: 828-842. PMID: 31983222, PMCID: PMC7077965, DOI: 10.1161/circulationaha.119.042339.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnimalsCardiac MyosinsCardiomyopathy, HypertrophicCells, CulturedEnergy MetabolismHumansInduced Pluripotent Stem CellsMiceMolecular Dynamics SimulationMuscle RelaxationMutation, MissenseMyocardial ContractionMyocytes, CardiacMyosin Heavy ChainsProtein ConformationSarcomeresConceptsProportion of myosinAdverse clinical outcomesHypertrophic cardiomyopathyHeart failureUnknown clinical significanceClinical outcomesClinical significancePathogenic variantsSarcomere functionSarcomere protein genesPathogenic missense variantsMyosin missense mutationsHemodynamic requirementsImpaired relaxationContractile abnormalitiesHealthy rodentsHypertrophic remodelingHemodynamic demandsPatient riskPoor relaxationCardiomyocyte contractilityHeart functionMyosin ATPase activityPatientsAllosteric modulators
2019
Extracellular Matrix From Hypertrophic Myocardium Provokes Impaired Twitch Dynamics in Healthy Cardiomyocytes
Sewanan LR, Schwan J, Kluger J, Park J, Jacoby DL, Qyang Y, Campbell SG. Extracellular Matrix From Hypertrophic Myocardium Provokes Impaired Twitch Dynamics in Healthy Cardiomyocytes. JACC Basic To Translational Science 2019, 4: 495-505. PMID: 31468004, PMCID: PMC6712054, DOI: 10.1016/j.jacbts.2019.03.004.Peer-Reviewed Original ResearchHypertrophic cardiomyopathySarcomeric gene mutationsMiniature swine modelPluripotent stem cell-derived cardiomyocytesExtracellular matrix abnormalitiesStem cell-derived cardiomyocytesPoor relaxationCell-derived cardiomyocytesHealthy cardiomyocytesExtracellular matrixMouse modelPharmacological correctionProlonged contractionSwine modelHealthy extracellular matrixMuscle contractionGene mutationsMatrix abnormalitiesTwitch dynamicsCardiomyocytesContractionCardiomyopathyTherapyMyocardiumAbnormalities