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
GSK-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 heartIncreased length-dependent activation of human engineered heart tissue after chronic treatment with alpha-1A-adrenergic agonist
Rupert C, Cortez-Toledo E, Lopez J, Chesler N, Simpson P, Campbell S, Baker A. Increased length-dependent activation of human engineered heart tissue after chronic treatment with alpha-1A-adrenergic agonist. Biophysical Journal 2022, 121: 397a-398a. DOI: 10.1016/j.bpj.2021.11.785.Peer-Reviewed Original Research