2023
Increased length-dependent activation of human engineered heart tissue after chronic α1A-adrenergic agonist treatment: testing a novel heart failure therapy
Rupert C, López J, Cortez-Toledo E, De la Cruz Cabrera O, Chesler N, Simpson P, Campbell S, Baker A. Increased length-dependent activation of human engineered heart tissue after chronic α1A-adrenergic agonist treatment: testing a novel heart failure therapy. AJP Heart And Circulatory Physiology 2023, 324: h293-h304. PMID: 36637971, PMCID: PMC9886349, DOI: 10.1152/ajpheart.00279.2022.Peer-Reviewed Original ResearchConceptsHuman heart failureHeart failureAR stimulationChronic stimulationLength-dependent activationVehicle treatmentHeart tissueAdrenergic receptorsHuman EHTsAnimal heart failure modelNovel heart failure therapiesHeart failure therapyHeart failure modelMultiple preclinical modelsFailure therapyAgonist treatmentSeparate control experimentsPreclinical modelsDrug washoutTherapeutic effectTranslational significanceHuman myocardiumBaseline testingRNA-seq analysisPig myocardium
2022
Signaling network model of cardiomyocyte morphological changes in familial cardiomyopathy
Khalilimeybodi A, Riaz M, Campbell S, Omens J, McCulloch A, Qyang Y, Saucerman J. Signaling network model of cardiomyocyte morphological changes in familial cardiomyopathy. Journal Of Molecular And Cellular Cardiology 2022, 174: 1-14. PMID: 36370475, PMCID: PMC10230857, DOI: 10.1016/j.yjmcc.2022.10.006.Peer-Reviewed Original ResearchHumanized Dsp ACM Mouse Model Displays Stress-Induced Cardiac Electrical and Structural Phenotypes
Stevens TL, Manring HR, Wallace MJ, Argall A, Dew T, Papaioannou P, Antwi-Boasiako S, Xu X, Campbell SG, Akar FG, Borzok MA, Hund TJ, Mohler PJ, Koenig SN, El Refaey M. Humanized Dsp ACM Mouse Model Displays Stress-Induced Cardiac Electrical and Structural Phenotypes. Cells 2022, 11: 3049. PMID: 36231013, PMCID: PMC9562631, DOI: 10.3390/cells11193049.Peer-Reviewed Original ResearchConceptsArrhythmogenic cardiomyopathyMouse modelStructural phenotypesFibro-fatty infiltrationFirst mouse modelHeart failureChamber dilationVentricular arrhythmiasPressure overloadArrhythmic eventsCardiac performanceCardiac stressSudden deathCardiovascular stressInherited disorderG variantConnexin 43MiceDesmosomal genesReduced expressionExternal stressorsACM familyDisease developmentMurine equivalentIncomplete penetranceGSK-3β Localizes to the Cardiac Z-Disc to Maintain Length Dependent Activation
Stachowski-Doll MJ, Papadaki M, Martin TG, Ma W, Gong HM, Shao S, Shen S, Muntu NA, Kumar M, Perez E, Martin JL, Moravec CS, Sadayappan S, Campbell SG, Irving T, Kirk JA. GSK-3β Localizes to the Cardiac Z-Disc to Maintain Length Dependent Activation. Circulation Research 2022, 130: 871-886. PMID: 35168370, PMCID: PMC8930626, DOI: 10.1161/circresaha.121.319491.Peer-Reviewed Original ResearchConceptsZ-discGSK-3βZ-disc proteinsCardiac Z-diskLength-dependent activationKnockout miceKinase localizationPhosphorylation sitesNegative regulatorGenetic knockdownVivo roleDependent activationNeonatal rat ventricular cardiomyocytesNovel mechanismGSK-3β levelsHeart failureMyofilament localizationTitin phosphorylationVentricular myocardiumPossible therapeutic targetTitin isoformsTitin stiffnessTherapeutic targetPassive tensionHuman heart