2022
Quantification of intramyocardial blood volume using 99mTc-RBC SPECT/CT: a pilot human study
Yousefi H, Shi L, Soufer A, Tsatkin V, Bruni W, Avendano R, Greco K, McMahon D, Thorn S, Miller E, Sinusas A, Liu C. Quantification of intramyocardial blood volume using 99mTc-RBC SPECT/CT: a pilot human study. Journal Of Nuclear Cardiology 2022, 30: 292-297. PMID: 36319815, DOI: 10.1007/s12350-022-03123-0.Peer-Reviewed Original ResearchDuDoSS: Deep‐learning‐based dual‐domain sinogram synthesis from sparsely sampled projections of cardiac SPECT
Chen X, Zhou B, Xie H, Miao T, Liu H, Holler W, Lin M, Miller EJ, Carson RE, Sinusas AJ, Liu C. DuDoSS: Deep‐learning‐based dual‐domain sinogram synthesis from sparsely sampled projections of cardiac SPECT. Medical Physics 2022, 50: 89-103. PMID: 36048541, PMCID: PMC9868054, DOI: 10.1002/mp.15958.Peer-Reviewed Original ResearchConceptsLow reconstruction accuracySynthetic projectionsAbsolute percent errorImage predictionSPECT image reconstructionImage domainSinogram synthesisGround truthReconstruction accuracyImage reconstructionSinogram domainProjection angleData acquisitionMean square errorFast data acquisitionImagesReconstruction artifactsSPECT imagesSquare error
2020
Feasibility study of PET dynamic imaging of [18F]DHMT for quantification of reactive oxygen species in the myocardium of large animals
Wu J, Boutagy NE, Cai Z, Lin SF, Zheng MQ, Feher A, Stendahl JC, Kapinos M, Gallezot JD, Liu H, Mulnix T, Zhang W, Lindemann M, Teng JK, Miller EJ, Huang Y, Carson RE, Sinusas AJ, Liu C. Feasibility study of PET dynamic imaging of [18F]DHMT for quantification of reactive oxygen species in the myocardium of large animals. Journal Of Nuclear Cardiology 2020, 29: 216-225. PMID: 32415628, PMCID: PMC7666654, DOI: 10.1007/s12350-020-02184-3.Peer-Reviewed Original ResearchComplex cellular physiology underlies the use of FDG-PET imaging in investigating post-infarction remodeling
Miller EJ. Complex cellular physiology underlies the use of FDG-PET imaging in investigating post-infarction remodeling. Journal Of Nuclear Cardiology 2020, 27: 532-533. PMID: 31907858, DOI: 10.1007/s12350-019-02008-z.Peer-Reviewed Original Research
2017
Up-regulation of Intracellular Calcium Handling Underlies the Recovery of Endotoxemic Cardiomyopathy in Mice
Morse JC, Huang J, Khona N, Miller EJ, Siwik DA, Colucci WS, Hobai IA. Up-regulation of Intracellular Calcium Handling Underlies the Recovery of Endotoxemic Cardiomyopathy in Mice. Anesthesiology 2017, 126: 1125-1138. PMID: 28410273, DOI: 10.1097/aln.0000000000001627.Peer-Reviewed Original ResearchConceptsCalcium transientsCardiac recoveryLipopolysaccharide challengeCalcium handlingDay 3Sarcomere shorteningCardiomyocyte calcium handlingSepsis-induced cardiomyopathyVentricular ejection fractionIntracellular calcium handlingSarcoplasmic reticulum calcium loadMale C57BL/6 miceSodium/calcium exchangeMyocardial protein expressionSarcoplasmic reticulum calcium pumpSystemic inflammationEjection fractionEndotoxemic miceC57BL/6 miceMyocardial mechanismsCardiac functionCalcium loadCardiac contractilityBaseline levelsDay 6
2016
Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet‐Induced Metabolic Heart Disease
Sverdlov AL, Elezaby A, Qin F, Behring JB, Luptak I, Calamaras TD, Siwik DA, Miller EJ, Liesa M, Shirihai OS, Pimentel DR, Cohen RA, Bachschmid MM, Colucci WS. Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet‐Induced Metabolic Heart Disease. Journal Of The American Heart Association 2016, 5: e002555. PMID: 26755553, PMCID: PMC4859372, DOI: 10.1161/jaha.115.002555.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCatalaseDiet, High-FatDietary SucroseDisease Models, AnimalElectron Transport Complex IElectron Transport Complex IIEnergy MetabolismHypertrophy, Left VentricularMice, Inbred C57BLMice, TransgenicMitochondria, HeartMitochondrial DiseasesMutationOxidation-ReductionOxidative StressProtein Processing, Post-TranslationalReactive Oxygen SpeciesVentricular Dysfunction, LeftVentricular Function, LeftConceptsOxidative posttranslational modificationsMitochondrial reactive oxygen speciesPosttranslational modificationsReactive oxygen speciesMetabolic heart diseaseATP synthesisMitochondrial dysfunctionCardiac mitochondrial proteinsSite-directed mutationsMitochondrial proteinsTransgenic miceWild-type miceComplex IMitochondriaMitochondrial abnormalitiesHigh palmitateOxygen speciesCardiac mitochondriaCys100Mitochondrial consequencesCys103Key mediatorProteinH2O2 productionHigh-fat high-sucrose diet
2015
Partial Liver Kinase B1 (LKB1) Deficiency Promotes Diastolic Dysfunction, De Novo Systolic Dysfunction, Apoptosis, and Mitochondrial Dysfunction With Dietary Metabolic Challenge
Miller EJ, Calamaras T, Elezaby A, Sverdlov A, Qin F, Luptak I, Wang K, Sun X, Vijay A, Croteau D, Bachschmid M, Cohen RA, Walsh K, Colucci WS. Partial Liver Kinase B1 (LKB1) Deficiency Promotes Diastolic Dysfunction, De Novo Systolic Dysfunction, Apoptosis, and Mitochondrial Dysfunction With Dietary Metabolic Challenge. Journal Of The American Heart Association 2015, 5: e002277. PMID: 26722122, PMCID: PMC4859355, DOI: 10.1161/jaha.115.002277.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsApoptosisApoptosis Regulatory ProteinsCaspase 3DiastoleDiet, High-FatDietary SucroseDisease Models, AnimalGenetic Predisposition to DiseaseHeterozygoteHypertrophy, Left VentricularMice, KnockoutMitochondria, HeartMyocardiumPhenotypeProtein Serine-Threonine KinasesSignal TransductionSystoleTime FactorsTumor Suppressor Protein p53Tumor Suppressor ProteinsVentricular Dysfunction, LeftVentricular Function, LeftVentricular RemodelingConceptsHigh-sucrose dietSystolic dysfunctionDiastolic dysfunctionLiver kinase B1Metabolic heart diseaseDietary excessHeart diseaseMyocardial hypertrophyDe novo appearanceControl dietRestrictive filling patternSevere diastolic dysfunctionLeft ventricular dilationMitochondrial dysfunctionMetabolic stressWild-type miceHigh-sucrose feedingNovo appearanceP53/PUMAMore hypertrophyDiastolic functionMyocardial dysfunctionVentricular hypertrophyVentricular dilationSevere mitochondrial dysfunctionAMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism
Sung MM, Zordoky BN, Bujak AL, Lally JS, Fung D, Young ME, Horman S, Miller EJ, Light PE, Kemp BE, Steinberg GR, Dyck JR. AMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism. Cardiovascular Research 2015, 107: 235-245. PMID: 26023060, PMCID: PMC4565988, DOI: 10.1093/cvr/cvv166.Peer-Reviewed Original ResearchConceptsHeart failureCardiac functionCardiac hypertrophyRole of AMPKAMPK deficiencyCompensatory cardiac hypertrophyWild-type littermatesFatty acid oxidation ratesMyocardial energy metabolismAlters cardiac functionMuscle-specific deletionFirst mouse modelDiastolic functionAbsence of changesCardiac dysfunctionWT miceBasal glucoseMyocardial functionMyocardial metabolismCell shorteningMouse modelCardiac muscle resultsHypertrophyImpaired activationTroponin I
2014
Mitochondrial remodeling in mice with cardiomyocyte-specific lipid overload
Elezaby A, Sverdlov AL, Tu VH, Soni K, Luptak I, Qin F, Liesa M, Shirihai OS, Rimer J, Schaffer JE, Colucci WS, Miller EJ. Mitochondrial remodeling in mice with cardiomyocyte-specific lipid overload. Journal Of Molecular And Cellular Cardiology 2014, 79: 275-283. PMID: 25497302, PMCID: PMC4301992, DOI: 10.1016/j.yjmcc.2014.12.001.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCarnitineCatalaseCeramidesCyclic AMP Response Element-Binding ProteinDiglyceridesElectron Transport Complex IIFatty Acid Transport ProteinsGene Expression RegulationHydrogen PeroxideLipidsMiceMitochondria, HeartModels, BiologicalMyocardiumMyocytes, CardiacOrgan SpecificityOxygen ConsumptionPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPhosphorylationPPAR alphaProtein Kinase CProto-Oncogene Proteins c-aktRNA, MessengerSphingomyelinsTranscription FactorsConceptsMetabolic heart diseaseMitochondrial structureMitochondrial fusion genes Mfn1Mitochondrial-targeted catalaseOverexpression of catalaseMitochondrial oxidative stressStructure/functionPhosphorylation of AktToxic metabolite accumulationTranscriptional regulationMitochondrial structure/functionFatty acid uptakeCardiomyocyte lipid accumulationMitochondrial remodelingMetabolite accumulationDiacylglycerol speciesExcess FAATP synthesisMitochondrial functionMitochondrial dysfunctionLipid speciesFA uptakeMitochondrial sizeHydrogen peroxide productionSubunit BHigh fat, high sucrose diet causes cardiac mitochondrial dysfunction due in part to oxidative post-translational modification of mitochondrial complex II
Sverdlov AL, Elezaby A, Behring JB, Bachschmid MM, Luptak I, Tu VH, Siwik DA, Miller EJ, Liesa M, Shirihai OS, Pimentel DR, Cohen RA, Colucci WS. High fat, high sucrose diet causes cardiac mitochondrial dysfunction due in part to oxidative post-translational modification of mitochondrial complex II. Journal Of Molecular And Cellular Cardiology 2014, 78: 165-173. PMID: 25109264, PMCID: PMC4268348, DOI: 10.1016/j.yjmcc.2014.07.018.Peer-Reviewed Original ResearchConceptsCysteine oxidative post-translational modificationsOxidative post-translational modificationsCardiac mitochondrial proteinsPost-translational modificationsMetabolic heart diseaseMitochondrial proteinsATP synthesisMitochondrial dysfunctionBasic Mitochondrial BiologyCardiac mitochondriaMitochondrial biologyOxidative stressTag labelingCardiac mitochondrial dysfunctionBiotin switchSubunit AATP productionMitochondrial ROSGSH/GSSG ratioFunctional consequencesMitochondriaReversible oxidationGSSG ratioProteinSDHAA novel LKB1 isoform enhances AMPK metabolic activity and displays oncogenic properties
Dahmani R, Just P, Delay A, Canal F, Finzi L, Prip-Buus C, Lambert M, Sujobert P, Buchet-Poyau K, Miller E, Cavard C, Marmier S, Terris B, Billaud M, Perret C. A novel LKB1 isoform enhances AMPK metabolic activity and displays oncogenic properties. Oncogene 2014, 34: 2337-2346. PMID: 24998845, DOI: 10.1038/onc.2014.182.Peer-Reviewed Original ResearchConceptsLKB1 tumor suppressor geneTumor suppressor genePolarizing activitySuppressor geneOncogenic propertiesN-terminal regionCell polarityMaster kinaseMetabolic activityAutoinhibitory domainAlternative transcriptionKinase domainNovel isoformMetabolic sensorSame locusInternal initiationLKB1LKB1 mRNANCI-H460 cellsEnergetic metabolismLung cancer cell linesCancer cell linesDirect interactionIsoformsCell lines
2013
Urocortin 2 autocrine/paracrine and pharmacologic effects to activate AMP-activated protein kinase in the heart
Li J, Qi D, Cheng H, Hu X, Miller EJ, Wu X, Russell KS, Mikush N, Zhang J, Xiao L, Sherwin RS, Young LH. Urocortin 2 autocrine/paracrine and pharmacologic effects to activate AMP-activated protein kinase in the heart. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 16133-16138. PMID: 24043794, PMCID: PMC3791748, DOI: 10.1073/pnas.1312775110.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl-CoA CarboxylaseAMP-Activated Protein KinasesAnalysis of VarianceAnimalsAntibodies, NeutralizingCorticotropin-Releasing HormoneEnzyme ActivationImmunoblottingImmunohistochemistryMiceMyocardiumPeptide FragmentsPhosphorylationReceptors, Corticotropin-Releasing HormoneReperfusion InjurySignal TransductionUrocortinsConceptsIschemia/reperfusionIschemia/reperfusion injuryUCN2 treatmentReperfusion injuryContractile dysfunctionRegional ischemia/reperfusionAMPK activationHeart muscleIschemic AMPK activationAutocrine/paracrine pathwayCardiac contractile dysfunctionAutocrine/paracrine factorCorticotropin-releasing factor (CRF) familyIsolated heart muscleCRFR2 antagonistAcetyl-CoA carboxylase phosphorylationCardiac damageMyocardial injuryCRF receptorsPharmacologic effectsUrocortin 2ΕV1-2Activation of AMPParacrine pathwaysReperfusion
2012
The Polyphenols Resveratrol and S17834 Prevent the Structural and Functional Sequelae of Diet-Induced Metabolic Heart Disease in Mice
Qin F, Siwik DA, Luptak I, Hou X, Wang L, Higuchi A, Weisbrod RM, Ouchi N, Tu VH, Calamaras TD, Miller EJ, Verbeuren TJ, Walsh K, Cohen RA, Colucci WS. The Polyphenols Resveratrol and S17834 Prevent the Structural and Functional Sequelae of Diet-Induced Metabolic Heart Disease in Mice. Circulation 2012, 125: 1757-1764. PMID: 22388319, PMCID: PMC3354628, DOI: 10.1161/circulationaha.111.067801.Peer-Reviewed Original ResearchConceptsHFHS diet-fed miceDiet-fed miceMetabolic heart diseaseDiastolic dysfunctionLeft ventricular hypertrophyMyocardial oxidative stressVentricular hypertrophyHeart diseaseInterstitial fibrosisPlasma adiponectinInsulin resistanceProgressive left ventricular hypertrophyDiet-induced metabolic syndromeBeneficial effectsOxidative stressHomeostasis model assessmentMale C57BL/6J miceChronic hemodynamic overloadHFHS dietCardiovascular effectsSystolic functionDiabetes mellitusMetabolic syndromeConcomitant treatmentHemodynamic overload
2011
A small molecule AMPK activator protects the heart against ischemia–reperfusion injury
Kim AS, Miller EJ, Wright TM, Li J, Qi D, Atsina K, Zaha V, Sakamoto K, Young LH. A small molecule AMPK activator protects the heart against ischemia–reperfusion injury. Journal Of Molecular And Cellular Cardiology 2011, 51: 24-32. PMID: 21402077, PMCID: PMC4005884, DOI: 10.1016/j.yjmcc.2011.03.003.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAMP-Activated Protein KinasesAnimalsApoptosisBiphenyl CompoundsCardiotonic AgentsEnzyme ActivatorsHeartIschemic PreconditioningMiceMice, Inbred C57BLMice, TransgenicMyocardial InfarctionMyocardial Reperfusion InjuryNecrosisNitric Oxide Synthase Type IIIPeptide Elongation Factor 2PyronesThiophenesConceptsIschemia-reperfusion injuryLeft ventricular contractile functionMyocardial ischemia-reperfusion injuryMouse heartsEndothelial nitric oxide synthase activationNitric oxide synthase activationLess myocardial necrosisCoronary artery occlusionIschemia-reperfusion damageVentricular contractile functionEukaryotic elongation factor 2Isolated mouse heartsPost-ischemic reperfusionAMPK activatorArtery occlusionIschemic contractureIschemic injuryInfarct sizeMyocardial stunningMyocardial necrosisCardioprotective mechanismsContractile functionSolid organsTherapeutic targetMyocardial apoptosis
2009
AMP‐activated protein kinase: a core signalling pathway in the heart
Kim AS, Miller EJ, Young LH. AMP‐activated protein kinase: a core signalling pathway in the heart. Acta Physiologica 2009, 196: 37-53. PMID: 19239414, DOI: 10.1111/j.1748-1716.2009.01978.x.BooksConceptsProtein kinaseEssential cellular processesTumor suppressor LKB1Downstream AMPK targetsProduction of ATPProtein phosphataseAMPK targetsActivated AMPKIntracellular glycogen accumulationCellular processesUpstream kinaseFatty acid metabolismCardiac myocyte hypertrophyAMPK activationAMPK activityImportant intracellularMolecular mechanismsMajor regulatorAMPKProtein synthesisKinaseAcid metabolismOral hypoglycaemic drugsGlycogen accumulationType 2 diabetes
2008
Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart
Miller EJ, Li J, Leng L, McDonald C, Atsumi T, Bucala R, Young LH. Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature 2008, 451: 578-582. PMID: 18235500, DOI: 10.1038/nature06504.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntigens, Differentiation, B-LymphocyteCoronary Artery DiseaseEnzyme ActivationGenetic Predisposition to DiseaseGenotypeGlucoseHistocompatibility Antigens Class IIHumansHypoxiaMacrophage Migration-Inhibitory FactorsMiceMultienzyme ComplexesMyocardial IschemiaMyocardial Reperfusion InjuryMyocardiumPolymorphism, GeneticPromoter Regions, GeneticProtein Serine-Threonine KinasesRatsSignal TransductionConceptsIschemic heartMacrophage migration inhibitory factorLower MIF levelsCoronary artery diseaseIschemic heart diseaseMigration inhibitory factorPotential risk markerMIF levelsArtery diseaseRisk markersHeart diseaseIschemic stressCytokine MIFInhibitory factorGlucose uptakePotential drug targetsDiseaseHeartDrug targetsCellular stress responseAMPKMaster regulatorNew studiesPatientsAtherosclerosis
2007
Infusion of a biotinylated bis-glucose photolabel: a new method to quantify cell surface GLUT4 in the intact mouse heart
Miller EJ, Li J, Sinusas KM, Holman GD, Young LH. Infusion of a biotinylated bis-glucose photolabel: a new method to quantify cell surface GLUT4 in the intact mouse heart. AJP Endocrinology And Metabolism 2007, 292: e1922-e1928. PMID: 17341550, DOI: 10.1152/ajpendo.00170.2006.Peer-Reviewed Original ResearchConceptsBio-LCCell surface GLUT4Glucose transporterSurface GLUT4Cell surface glucose transportersGlucose transporter contentCell surface GLUT1Glucose transporter GLUT4Intracellular storage vesiclesMouse heartsTransporter contentSpecific glucose transportersCell surface membraneGlucose uptakeCell surface contentMolecular regulationIntact mouse heartsGLUT4Cell surfaceStorage vesiclesGlucose transportMetabolic stressTransgenic mouse heartsSurface membraneTransporters
2006
Activation of AMPK α- and γ-isoform complexes in the intact ischemic rat heart
Li J, Coven DL, Miller EJ, Hu X, Young ME, Carling D, Sinusas AJ, Young LH. Activation of AMPK α- and γ-isoform complexes in the intact ischemic rat heart. AJP Heart And Circulatory Physiology 2006, 291: h1927-h1934. PMID: 16648175, DOI: 10.1152/ajpheart.00251.2006.Peer-Reviewed Original ResearchConceptsAMPK activityAMPK complexAlpha subunit activationDifferent subunit isoformsSerine-threonine kinaseCellular metabolic processesGamma subunit isoformsRegulatory betaAlpha-subunit contentHeterotrimeric complexProtein kinaseAMPK αMultiple isoformsKinase activitySubunit isoformsMetabolic processesAMPK phosphorylationAMPKIsoformsPhysiological regulationKinaseMutationsComplexesKey rolePathophysiological importance
2005
AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart
Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR, Young LH. AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart. Circulation Research 2005, 97: 872-879. PMID: 16179588, DOI: 10.1161/01.res.0000187458.77026.10.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsAnisomycinCell HypoxiaEnzyme ActivationGlucoseGlucose Transporter Type 4Intracellular Signaling Peptides and ProteinsMaleMAP Kinase Kinase 3MiceMice, Inbred C57BLMice, TransgenicMultienzyme ComplexesMyocardial IschemiaP38 Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesProtein TransportRatsRats, Sprague-DawleyRibonucleotidesConceptsMitogen-activated protein kinaseP38 mitogen-activated protein kinaseMAPK kinase 3P38 MAPK activationAlpha2 catalytic subunitProtein kinaseMAPK activationCatalytic subunitGlucose transportStress-signaling pathwaysAMPK activator 5Role of AMPKProtein kinase 1Direct molecular targetP38 MAPK inhibitorMouse heartsAMPK complexProtein TAB1Scaffold proteinGLUT4 translocationUpstream kinaseAMPK activationKinase 3Kinase 1MAPK inhibitorDual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart
Baron SJ, Li J, Russell RR, Neumann D, Miller EJ, Tuerk R, Wallimann T, Hurley RL, Witters LA, Young LH. Dual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart. Circulation Research 2005, 96: 337-345. PMID: 15653571, DOI: 10.1161/01.res.0000155723.53868.d2.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine MonophosphateAdenosine TriphosphateAminoimidazole CarboxamideAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsInfusions, IntravenousMaleMultienzyme ComplexesMyocardial IschemiaMyocardiumPhosphorylationProtein KinasesProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyRecombinant ProteinsRibonucleotidesConceptsRecombinant AMPKAMPKK activityAMPK phosphorylationPhosphorylation of Thr172Gamma regulatory subunitsIschemic heartImportant signaling proteinAlpha catalytic subunitRat heartHeterotrimeric AMPKAMPKKHeterotrimeric complexActivation loopRegulatory subunitKinase actionSignaling proteinsCatalytic subunitProtein kinaseAMPK activityLow-flow ischemiaGamma subunitsAMPKInteraction of AMPPhosphorylationAddition of AMP