2023
PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation
Perike S, Gonzalez-Gonzalez F, Abu-Taha I, Damen F, Hanft L, Lizama K, Aboonabi A, Capote A, Aguilar-Sanchez Y, Levin B, Han Z, Sridhar A, Grand J, Martin J, Akar J, Warren C, Solaro R, Ong S, Darbar D, McDonald K, Goergen C, Wolska B, Dobrev D, Wehrens X, McCauley M. PPP1R12C Promotes Atrial Hypocontractility in Atrial Fibrillation. Circulation Research 2023, 133: 758-771. PMID: 37737016, PMCID: PMC10616980, DOI: 10.1161/circresaha.123.322516.Peer-Reviewed Original ResearchConceptsSinus rhythm controlsAtrial hypocontractilityAF inducibilityAtrial contractilityAtrial fibrillationRhythm controlHuman patientsRight atrial appendage tissuePacing-induced AFThromboembolic stroke riskAtrial ejection fractionAtrial appendage tissueAtrial HL-1 cellsHL-1 cellsAtrial strainStroke riskAtrial sizeEjection fractionContractile functionElectrophysiology studyHypocontractilityWestern blotPatientsAtrial myosin light chainSarcomere function
2021
Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment
Pettinato A, Yoo D, VanOudenhove J, Chen Y, Cohn R, Ladha F, Yang X, Thakar K, Romano R, Legere N, Meredith E, Robson P, Regnier M, Cotney J, Murry C, Hinson J. Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment. Cell Reports 2021, 35: 109088. PMID: 33951429, PMCID: PMC8161465, DOI: 10.1016/j.celrep.2021.109088.Peer-Reviewed Original ResearchConceptsCell cycle arrestSarcomere functionHuman cardiomyocyte modelHuman cardiac regenerationInfarcted rat heartsCardiomyocyte engraftmentCell engraftmentReplicative rateRat heartDNA damage responseCardiomyocyte modelCardiac regenerationOxidative metabolismUnclear mechanismsProgressive polyploidizationCyclin B1P53-dependent DNA damage responseEngraftmentP53 activationArrestDamage responseSingle-cell transcriptomicsReplicative arrest
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
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